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UniProtKB/Swiss-Prot entry P08473


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

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Entry information
Entry name NEP_HUMAN
Primary accession number P08473
Secondary accession number Q3MIX4
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 117)
Name and origin of the protein
Protein name Neprilysin
Synonyms EC 3.4.24.11
Neutral endopeptidase 24.11
Neutral endopeptidase
NEP
Enkephalinase
Atriopeptidase
Common acute lymphocytic leukemia antigen
CALLA
CD10 antigen
Gene name
Name: MME
Synonyms: EPN
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] OF 3-750.
TISSUE=Placenta;
DOI=10.1016/0014-5793(88)80828-7; PubMed=3162217 [NCBI, ExPASy, EBI, Israel, Japan]
Malfroy B., Kuang W.-J., Seeburg P.H., Mason A.J., Schofield P.R.;
"Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase).";
FEBS Lett. 229:206-210(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Kidney;
DOI=10.1084/jem.168.4.1247; PubMed=2971756 [NCBI, ExPASy, EBI, Israel, Japan]
Letarte M., Vera S., Tran R., Addis J.B.L., Onizuka R.J., Quackenbush E.J., Jongeneel C.V., McInnes R.R.;
"Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase.";
J. Exp. Med. 168:1247-1253(1988).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2968607 [NCBI, ExPASy, EBI, Israel, Japan]
Shipp M.A., Richardson N.E., Sayre P.H., Brown N.R., Masteller E.L., Clayton L.K., Ritz J., Reinherz E.L.;
"Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein.";
Proc. Natl. Acad. Sci. U.S.A. 85:4819-4823(1988).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2528730 [NCBI, ExPASy, EBI, Israel, Japan]
D'Adamio L., Shipp M.A., Masteller E.L., Reinherz E.L.;
"Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions.";
Proc. Natl. Acad. Sci. U.S.A. 86:7103-7107(1989).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
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).
[6]
FUNCTION IN THE DEGRADATION ANF.
DOI=10.1016/0196-9781(89)90131-9; PubMed=2531377 [NCBI, ExPASy, EBI, Israel, Japan]
Yandle T.G., Brennan S.O., Espiner E.A., Nicholls M.G., Richards A.M.;
"Endopeptidase-24.11 in human plasma degrades atrial natriuretic factor (ANF) to ANF(99-105/106-126).";
Peptides 10:891-894(1989).
[7]
ACTIVE SITE ASP-651.
PubMed=8168535 [NCBI, ExPASy, EBI, Israel, Japan]
Le Moual H., Dion N., Roques B.P., Crine P., Boileau G.;
"Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11.";
Eur. J. Biochem. 221:475-480(1994).
[8]
GLYCOSYLATION AT ASN-145 AND ASN-285.
DOI=10.1038/nbt827; PubMed=12754519 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang H., Li X.-J., Martin D.B., Aebersold R.;
"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.";
Nat. Biotechnol. 21:660-666(2003).
[9]
INHIBITION BY OPIORPHIN.
DOI=10.1073/pnas.0605865103; PubMed=17101991 [NCBI, ExPASy, EBI, Israel, Japan]
Wisner A., Dufour E., Messaoudi M., Nejdi A., Marcel A., Ungeheuer M.-N., Rougeot C.;
"Human opiorphin, a natural antinociceptive modulator of opioid-depentent pathways.";
Proc. Natl. Acad. Sci. U.S.A. 103:17979-17984(2006).
[10]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND GLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.
DOI=10.1006/jmbi.1999.3492; PubMed=10669592 [NCBI, ExPASy, EBI, Israel, Japan]
Oefner C., D'Arcy A., Hennig M., Winkler F.K., Dale G.E.;
"Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon.";
J. Mol. Biol. 296:341-349(2000).
Comments
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
X07166; CAA30157.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Y00811; CAA68752.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J03779; AAA51915.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26628; AAA52294.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26607; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26608; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26609; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26610; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26611; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26612; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26613; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26614; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26615; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26616; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26617; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26618; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26619; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26620; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26621; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26622; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26623; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26624; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26625; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26626; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26627; AAA52294.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC101632; AAI01633.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC101658; AAI01659.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A41387; HYHUN.
RefSeq NP_000893.2; -.
NP_009218.2; -.
NP_009219.2; -.
NP_009220.2; -.
UniGene Hs.307734
3D structure databases
PDB
1DL9; Model; -; A=508-750.[ExPASy / RCSB / EBI]
1DMT; X-ray; 2.10 A; A=55-750.[ExPASy / RCSB / EBI]
1QVD; Model; -; A=55-750.[ExPASy / RCSB / EBI]
1R1H; X-ray; 1.95 A; A=55-750.[ExPASy / RCSB / EBI]
1R1I; X-ray; 2.60 A; A=55-750.[ExPASy / RCSB / EBI]
1R1J; X-ray; 2.35 A; A=55-750.[ExPASy / RCSB / EBI]
1Y8J; X-ray; 2.25 A; A=55-750.[ExPASy / RCSB / EBI]
2QPJ; X-ray; 2.05 A; A=55-750.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1DL9; -.
1DMT; -.
1QVD; -.
1R1H; -.
1R1I; -.
1R1J; -.
1Y8J; -.
2QPJ; -.
ModBase P08473.
Protein-protein interaction databases
IntAct P08473; -.
Protein family/group databases
MEROPS M13.001; -.
PTM databases
PhosphoSite P08473; -.
Organism-specific databases
H-InvDB HIX0003792; -.
HGNC HGNC:7154; MME.
GenAtlas MME.
HPA CAB000013; -.
MIM 120520; gene. [NCBI / EBI]
PharmGKB PA30864; -.
GeneCards P08473.
Gene expression databases
ArrayExpress P08473; -.
CleanEx HS_MME; -.
GermOnline ENSG00000196549; Homo sapiens.
Ontologies
GO
GO:0005887; Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0008237; Molecular function: metallopeptidase activity (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0007267; Biological process: cell-cell signaling (traceable author statement from ProtInc).
GO:0006508; Biological process: proteolysis (traceable author statement from ProtInc).
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 P08473.
ProtoNet P08473.
Proteomic databases
PeptideAtlas P08473; -.
Genome annotation databases
Ensembl ENSG00000196549; Homo sapiens. [Contig view]
GeneID 4311; -.
KEGG hsa:4311; -.
Phylogenomic databases
HOGENOM P08473; -.
HOVERGEN P08473; -.
Other
DrugBank DB00616; Candoxatril.
NextBio 16959; -.
SOURCE MME; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; 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_0000078213
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   591   591         
ACT_SITE   651   651        Proton donor. 
METAL   584   584        Zinc; catalytic. 
METAL   588   588        Zinc; catalytic. 
METAL   647   647        Zinc; catalytic. 
BINDING   103   103        Substrate carboxyl (By similarity). 
CARBOHYD   145   145        N-linked (GlcNAc...). 
CARBOHYD   285   285        N-linked (GlcNAc...). 
CARBOHYD   325   325        N-linked (GlcNAc...). 
CARBOHYD   628   628        N-linked (GlcNAc...). 
DISULFID   57    62         
DISULFID   80   735         
DISULFID   88   695         
DISULFID   143   411         
DISULFID   234   242         
DISULFID   621   747         
CONFLICT   26    26        P -> R (in Ref. 3; AAA51915). 
CONFLICT   44    44        T -> R (in Ref. 3; AAA51915). 
CONFLICT   81    81        T -> R (in Ref. 3; AAA51915). 
CONFLICT   304   304        T -> R (in Ref. 3; AAA51915). 
HELIX   60    72  13      
TURN   79    81  3      
HELIX   83    94  12      
STRAND   102   105  4      
HELIX   106   122  17      
HELIX   131   144  14      
HELIX   146   151  6      
TURN   152   154  3      
HELIX   155   160  6      
HELIX   161   164  4      
HELIX   168   170  3      
HELIX   174   177  4      
TURN   178   181  4      
HELIX   184   195  12      
STRAND   200   208  9      
STRAND   211   220  10      
STRAND   225   228  4      
HELIX   229   233  5      
HELIX   236   238  3      
HELIX   239   259  21      
HELIX   266   286  21      
HELIX   290   292  3      
HELIX   296   299  4      
STRAND   302   304  3      
HELIX   305   311  7      
HELIX   323   331  9      
HELIX   332   334  3      
STRAND   343   347  5      
HELIX   349   359  11      
HELIX   364   379  16      
HELIX   380   382  3      
HELIX   385   389  5      
HELIX   392   399  8      
HELIX   407   418  12      
HELIX   420   431  12      
HELIX   436   457  22      
HELIX   463   475  13      
STRAND   477   482  6      
HELIX   485   488  4      
HELIX   490   496  7      
TURN   497   499  3      
HELIX   507   523  17      
TURN   524   527  4      
STRAND   545   547  3      
TURN   548   551  4      
STRAND   552   556  5      
HELIX   557   559  3      
TURN   562   564  3      
HELIX   571   576  6      
HELIX   578   587  10      
HELIX   588   590  3      
HELIX   594   596  3      
HELIX   609   627  19      
HELIX   632   634  3      
TURN   641   644  4      
HELIX   645   669  25      
HELIX   682   693  12      
STRAND   696   698  3      
HELIX   700   709  10      
HELIX   715   724  10      
HELIX   727   732  6      
Sequence information
Length: 750 AA [This is the length of the unprocessed precursor] Molecular weight: 85514 Da [This is the MW of the unprocessed precursor] CRC64: BCF3827C39898630 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 

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

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKALY RSCINESAID SRGGEPLLKL LPDIYGWPVA 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 
NKMTLAQIQN 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 

P08473 in FASTA format

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