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Protein

Neprilysin

Gene

MME

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

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

GO - Molecular functioni

  1. metalloendopeptidase activity Source: UniProtKB
  2. peptide binding Source: UniProtKB
  3. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-amyloid metabolic process Source: UniProtKB
  2. cellular response to cytokine stimulus Source: UniProtKB
  3. cellular response to UV-A Source: UniProtKB
  4. cellular response to UV-B Source: UniProtKB
  5. creatinine metabolic process Source: UniProtKB
  6. kidney development Source: UniProtKB
  7. peptide metabolic process Source: UniProtKB
  8. proteolysis Source: UniProtKB
  9. replicative senescence Source: UniProtKB
  10. sensory perception of pain Source: UniProtKB
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
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
ProteomesiUP000001595 Componenti: Chromosome 3

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

  1. axon Source: UniProtKB
  2. brush border Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. dendrite Source: UniProtKB
  5. extracellular vesicular exosome Source: Ensembl
  6. focal adhesion Source: Ensembl
  7. integral component of membrane Source: UniProtKB-KW
  8. neuron projection terminus Source: UniProtKB
  9. plasma membrane Source: UniProtKB
  10. synapse Source: UniProtKB
  11. synaptic vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 750749NeprilysinPRO_0000319885Add
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...)Sequence Analysis
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
Glycosylationi325 – 3251N-linked (GlcNAc...)Sequence Analysis
Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi621 ↔ 747By similarity
Glycosylationi628 – 6281N-linked (GlcNAc...)Sequence Analysis

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

Structurei

3D structure databases

ProteinModelPortaliQ5RE69.
SMRiQ5RE69. 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

GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ5RE69.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
TreeFamiTF315192.

Family and domain databases

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.

Q5RE69-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA
60 70 80 90 100
TYDDGICKSS DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET
110 120 130 140 150
SSRYGNFDIL RDELEVVLKD VLQEPKTEDI VAVQKAKTLY RSCINESAID
160 170 180 190 200
SRGGEPLLKL LPDVYGWPVA TENWEQKYGA SWTAEKAIAQ LNSKYGKKVL
210 220 230 240 250
INLFVGTDDK NSVNHVIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
260 270 280 290 300
SVARLIRQEE RLPIDENQLA LEMNKVMELE KEIANATAKP EDRNDPMLLY
310 320 330 340 350
KKMTLAQIQN NFSLEINGKP FSWLNFTNEI MSTVNISITN EEDVVVYAPE
360 370 380 390 400
YLTKLKPILT KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG
410 420 430 440 450
TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV
460 470 480 490 500
FIQTLDDLTW MDAETKKRAE EKALAIKERI GYPDDIVSND NKLNNEYLEL
510 520 530 540 550
NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR
560 570 580 590 600
NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
610 620 630 640 650
GDLVDWWTQQ SASNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA
660 670 680 690 700
DNGGLGQAYR AYQNYIKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP
710 720 730 740 750
EYAVNSIKTD VHSPGNFRII GTLQNSAEFS EAFHCRKNSY MNPEKKCRVW
Length:750
Mass (Da):85,514
Last modified:February 26, 2008 - v2
Checksum:iC4D1216E8361352F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti115 – 1151E → G in CAH89405 (Ref. 1) Curated
Sequence conflicti175 – 1751E → K in CAH89405 (Ref. 1) Curated
Sequence conflicti523 – 5231L → P in CAH89938 (Ref. 1) Curated
Sequence conflicti681 – 6811N → S in CAH92963 (Ref. 1) Curated
Sequence conflicti729 – 7291F → C in CAH92963 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857100 mRNA. Translation: CAH89405.1.
CR857668 mRNA. Translation: CAH89938.1.
CR860855 mRNA. Translation: CAH92963.1.
RefSeqiNP_001126748.1. NM_001133276.1.

Genome annotation databases

EnsembliENSPPYT00000016535; ENSPPYP00000015904; ENSPPYG00000014224.
GeneIDi100173750.
KEGGipon:100173750.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857100 mRNA. Translation: CAH89405.1.
CR857668 mRNA. Translation: CAH89938.1.
CR860855 mRNA. Translation: CAH92963.1.
RefSeqiNP_001126748.1. NM_001133276.1.

3D structure databases

ProteinModelPortaliQ5RE69.
SMRiQ5RE69. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM13.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSPPYT00000016535; ENSPPYP00000015904; ENSPPYG00000014224.
GeneIDi100173750.
KEGGipon:100173750.

Organism-specific databases

CTDi4311.

Phylogenomic databases

GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ5RE69.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
TreeFamiTF315192.

Family and domain databases

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...

Publicationsi

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

Entry informationi

Entry nameiNEP_PONAB
AccessioniPrimary (citable) accession number: Q5RE69
Secondary accession number(s): Q5R5K3, Q5RFQ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: March 4, 2015
This is version 65 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

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.