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UniProtKB/Swiss-Prot entry P07861


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NEP_RAT
Primary accession number P07861
Secondary accession numbers None
Integrated into Swiss-Prot on August 1, 1988
Sequence was last modified on January 23, 2007 (Sequence version 2)
Annotations were last modified on    November 4, 2008 (Entry version 81)
Name and origin of the protein
Protein name Neprilysin
Synonyms EC 3.4.24.11
Neutral endopeptidase 24.11
Neutral endopeptidase
NEP
Enkephalinase
Atriopeptidase
CD10 antigen
Gene name
Name: Mme
From
Rattus norvegicus (Rat) [TaxID: 10116] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
DOI=10.1016/S0006-291X(87)80475-8; PubMed=3555489 [NCBI, ExPASy, EBI, Israel, Japan]
Malfroy B., Schofield P.R., Kuang W.-J., Seeburg P.H., Mason A.J., Henzel W.J.;
"Molecular cloning and amino acid sequence of rat enkephalinase.";
Biochem. Biophys. Res. Commun. 144:59-66(1987).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Kidney;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
ACTIVE SITE ARG-103.
PubMed=2703483 [NCBI, ExPASy, EBI, Israel, Japan]
Bateman R.C. Jr., Jackson D., Slaughter C.A., Unnithan S., Chai Y.G., Moomaw C., Hersh L.B.;
"Identification of the active-site arginine in rat neutral endopeptidase 24.11 (enkephalinase) as arginine 102 and analysis of a glutamine 102 mutant.";
J. Biol. Chem. 264:6151-6157(1989).
[4]
INHIBITION BY SIALORPHIN.
DOI=10.1073/pnas.1431850100; PubMed=12835417 [NCBI, ExPASy, EBI, Israel, Japan]
Rougeot C., Messaoudi M., Hermitte V., Rigault A.G., Blisnick T., Dugave C., Desor D., Rougeon F.;
"Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity.";
Proc. Natl. Acad. Sci. U.S.A. 100:8549-8554(2003).
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. Involved in the degradation of atrial natriuretic factor (ANF).
  • CATALYTIC ACTIVITY: Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
  • COFACTOR: Binds 1 zinc ion per subunit.
  • ENZYME REGULATION: Inhibited in a dose dependent manner by sialorphin.
  • SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
  • SIMILARITY: Belongs to the peptidase M13 family [view classification].
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M15944; AAA41116.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC085753; AAH85753.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A29295; HYRTN.
RefSeq NP_036740.1; -.
UniGene Rn.33598
3D structure databases
HSSP P08473; 1DMT. [HSSP ENTRY / PDB]
SMR P07861; 55-750.
ModBase P07861.
Protein family/group databases
MEROPS M13.001; -.
Organism-specific databases
RGD 3098; Mme.
Gene expression databases
ArrayExpress P07861; -.
GermOnline ENSRNOG00000009514; Rattus norvegicus.
Ontologies
GO
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR006025; Pept_M_Zn_BS.
IPR000718; Peptidase_M13.
IPR008753; Peptidase_M13_N.
Graphical view of domain structure.
PANTHER PTHR11733; Peptidase_M13; 1.
Pfam PF01431; Peptidase_M13; 1.
PF05649; Peptidase_M13_N; 1.
Pfam graphical view of domain structure.
PRINTS PR00786; NEPRILYSIN.
PROSITE PS00142; ZINC_PROTEASE; 1.
BLOCKS P07861.
ProtoNet P07861.
Genome annotation databases
Ensembl ENSRNOG00000009514; Rattus norvegicus. [Contig view]
GeneID 24590; -.
KEGG rno:24590; -.
Phylogenomic databases
HOVERGEN P07861; -.
Other
NextBio 603776; -.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Direct protein sequencing; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease; Signal-anchor; Transmembrane; Zinc.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   750  749     Neprilysin. PRO_0000078217
TOPO_DOM   2    28  27     Cytoplasmic (Potential). 
TRANSMEM   29    51  23     Signal-anchor for type II membrane protein (Potential). 
TOPO_DOM   52   750  699     Extracellular (Potential). 
MOTIF   16    23  8     Stop-transfer sequence (Potential). 
ACT_SITE   585   585        By similarity. 
ACT_SITE   651   651        Proton donor (By similarity). 
METAL   584   584        Zinc; catalytic (By similarity). 
METAL   588   588        Zinc; catalytic (By similarity). 
METAL   647   647        Zinc; catalytic (By similarity). 
BINDING   103   103        Substrate carboxyl. 
CARBOHYD   145   145        N-linked (GlcNAc...) (By similarity). 
CARBOHYD   211   211        N-linked (GlcNAc...) (Potential). 
CARBOHYD   285   285        N-linked (GlcNAc...) (Potential). 
CARBOHYD   311   311        N-linked (GlcNAc...). 
CARBOHYD   325   325        N-linked (GlcNAc...) (By similarity). 
CARBOHYD   628   628        N-linked (GlcNAc...) (By similarity). 
DISULFID   57    62        By similarity. 
DISULFID   80   735        By similarity. 
DISULFID   88   695        By similarity. 
DISULFID   143   411        By similarity. 
DISULFID   234   242        By similarity. 
DISULFID   621   747        By similarity. 
Sequence information
Length: 750 AA [This is the length of the unprocessed precursor] Molecular weight: 85795 Da [This is the MW of the unprocessed precursor] CRC64: 609D4716C4B15CBC [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 

        70         80         90        100        110        120 
DCIKSAARLI QNMDASAEPC TDFFKYACGG WLKRNVIPET SSRYSNFDIL RDELEVILKD 

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGQPLLTL LPDIYGWPVA SQNWEQTYGT 

       190        200        210        220        230        240 
SWTAEKSIAQ LNSKYGKKVL INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE 

       250        260        270        280        290        300 
ACTAYVDFMI SVARLIRQEQ RLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 

       310        320        330        340        350        360 
NKMTLAKLQN NFSLEINGKP 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 NYKEEEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 

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

       610        620        630        640        650        660 
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFT WDLAGGQHLN GINTLGENIA DNGGIGQAYR 

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

       730        740        750 
GTLQNSAEFA DAFHCRKNSY MNPERKCRVW 

P07861 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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