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Q5RE69 (NEP_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 59. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length750 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 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 By similarity.

Subcellular location

Cell membrane; Single-pass type II membrane protein By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the peptidase M13 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Myristate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-amyloid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

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

peptide metabolic process

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 sequence or structural similarity. Source: UniProtKB

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

brush border

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection terminus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from sequence or structural similarity. Source: UniProtKB

synaptic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionmetalloendopeptidase 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 750749Neprilysin
PRO_0000319885

Regions

Topological domain2 – 2827Cytoplasmic Potential
Transmembrane29 – 5123Helical; Signal-anchor for type II membrane protein; Potential
Topological domain52 – 750699Extracellular Potential
Motif16 – 238Stop-transfer sequence Potential

Sites

Active site5851 By similarity
Active site6511Proton donor By similarity
Metal binding5841Zinc; catalytic By similarity
Metal binding5881Zinc; catalytic By similarity
Metal binding6471Zinc; catalytic By similarity
Binding site1031Substrate carboxyl By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine By similarity
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3251N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 62 By similarity
Disulfide bond80 ↔ 735 By similarity
Disulfide bond88 ↔ 695 By similarity
Disulfide bond143 ↔ 411 By similarity
Disulfide bond234 ↔ 242 By similarity
Disulfide bond621 ↔ 747 By similarity

Experimental info

Sequence conflict1151E → G in CAH89405. Ref.1
Sequence conflict1751E → K in CAH89405. Ref.1
Sequence conflict5231L → P in CAH89938. Ref.1
Sequence conflict6811N → S in CAH92963. Ref.1
Sequence conflict7291F → C in CAH92963. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q5RE69 [UniParc].

Last modified February 26, 2008. Version 2.
Checksum: C4D1216E8361352F

FASTA75085,514
        10         20         30         40         50         60 
MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 

        70         80         90        100        110        120 
DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET SSRYGNFDIL RDELEVVLKD 

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGEPLLKL LPDVYGWPVA TENWEQKYGA 

       190        200        210        220        230        240 
SWTAEKAIAQ LNSKYGKKVL INLFVGTDDK NSVNHVIHID QPRLGLPSRD YYECTGIYKE 

       250        260        270        280        290        300 
ACTAYVDFMI SVARLIRQEE RLPIDENQLA LEMNKVMELE KEIANATAKP EDRNDPMLLY 

       310        320        330        340        350        360 
KKMTLAQIQN NFSLEINGKP FSWLNFTNEI MSTVNISITN EEDVVVYAPE YLTKLKPILT 

       370        380        390        400        410        420 
KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG TTSETATWRR CANYVNGNME 

       430        440        450        460        470        480 
NAVGRLYVEA AFAGESKHVV EDLIAQIREV FIQTLDDLTW MDAETKKRAE EKALAIKERI 

       490        500        510        520        530        540 
GYPDDIVSND NKLNNEYLEL NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 

       550        560        570        580        590        600 
VVNAFYSSGR NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 

       610        620        630        640        650        660 
GDLVDWWTQQ SASNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA DNGGLGQAYR 

       670        680        690        700        710        720 
AYQNYIKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP EYAVNSIKTD VHSPGNFRII 

       730        740        750 
GTLQNSAEFS EAFHCRKNSY MNPEKKCRVW 

« Hide

References

[1]The German cDNA consortium
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR857100 mRNA. Translation: CAH89405.1.
CR857668 mRNA. Translation: CAH89938.1.
CR860855 mRNA. Translation: CAH92963.1.
RefSeqNP_001126748.1. NM_001133276.1.

3D structure databases

ProteinModelPortalQ5RE69.
SMRQ5RE69. Positions 55-750.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSM13.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSPPYT00000016535; ENSPPYP00000015904; ENSPPYG00000014224.
GeneID100173750.
KEGGpon:100173750.

Organism-specific databases

CTD4311.

Phylogenomic databases

GeneTreeENSGT00650000093248.
HOGENOMHOG000245574.
HOVERGENHBG005554.
InParanoidQ5R5K3.
KOK01389.
OMAVWCGTYR.
OrthoDBEOG7PZRWQ.
TreeFamTF315192.

Family and domain databases

Gene3D3.40.390.10. 2 hits.
InterProIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERPTHR11733. PTHR11733. 1 hit.
PfamPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSPR00786. NEPRILYSIN.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameNEP_PONAB
AccessionPrimary (citable) accession number: Q5RE69
Secondary accession number(s): Q5R5K3, Q5RFQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: April 16, 2014
This is version 59 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries