Reviewed,
UniProtKB/Swiss-Prot P07861 (NEP_RAT)
Last modified
June 16, 2009.
Version 89.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Neprilysin EC=3.4.24.11 Alternative name(s): Neutral endopeptidase 24.11 Short name=Neutral endopeptidase Short name=NEP Enkephalinase Atriopeptidase CD_antigen=CD10 | ||
| Gene names |
| ||
| Organism | Rattus norvegicus (Rat) | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 750 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein 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. 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 | |
| Sequence similarities | Belongs to the peptidase M13 family. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cell membrane Membrane |
| Domain | Signal-anchor Transmembrane |
| Ligand | Metal-binding Zinc |
| Molecular function | Hydrolase Metalloprotease Protease |
| PTM | Disulfide bond Glycoprotein |
| Technical term | Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | peptide metabolic process Inferred from mutant phenotype. Source: RGD proteolysisInferred from direct assay. Source: RGD |
| Cellular component | integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fractionInferred from direct assay. Source: RGD plasma membraneInferred from mutant phenotype. Source: RGD |
| Molecular function | metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro peptide bindingInferred from direct assay. Source: RGD zinc ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||||
| Chain | 2 – 750 | 749 | Neprilysin | PRO_0000078217 | |||||||
Regions | |||||||||||
| Topological domain | 2 – 28 | 27 | Cytoplasmic Potential | ||||||||
| Transmembrane | 29 – 51 | 23 | Signal-anchor for type II membrane protein Potential | ||||||||
| Topological domain | 52 – 750 | 699 | Extracellular Potential | ||||||||
| Motif | 16 – 23 | 8 | Stop-transfer sequence Potential | ||||||||
Sites | |||||||||||
| Active site | 585 | 1 | By similarity | ||||||||
| Active site | 651 | 1 | Proton donor By similarity | ||||||||
| Metal binding | 584 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 588 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 647 | 1 | Zinc; catalytic By similarity | ||||||||
| Binding site | 103 | 1 | Substrate carboxyl | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 145 | 1 | N-linked (GlcNAc...) By similarity | ||||||||
| Glycosylation | 211 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 285 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 311 | 1 | N-linked (GlcNAc...) Ref.1 | ||||||||
| Glycosylation | 325 | 1 | N-linked (GlcNAc...) By similarity | ||||||||
| Glycosylation | 628 | 1 | N-linked (GlcNAc...) By similarity | ||||||||
| Disulfide bond | 57 ↔ 62 | By similarity | |||||||||
| Disulfide bond | 80 ↔ 735 | By similarity | |||||||||
| Disulfide bond | 88 ↔ 695 | By similarity | |||||||||
| Disulfide bond | 143 ↔ 411 | By similarity | |||||||||
| Disulfide bond | 234 ↔ 242 | By similarity | |||||||||
| Disulfide bond | 621 ↔ 747 | By similarity | |||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and amino acid sequence of rat enkephalinase." Malfroy B., Schofield P.R., Kuang W.-J., Seeburg P.H., Mason A.J., Henzel W.J. Biochem. Biophys. Res. Commun. 144:59-66(1987) [PubMed: 3555489] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. |
| [2] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney. |
| [3] | "Identification of the active-site arginine in rat neutral endopeptidase 24.11 (enkephalinase) as arginine 102 and analysis of a glutamine 102 mutant." Bateman R.C. Jr., Jackson D., Slaughter C.A., Unnithan S., Chai Y.G., Moomaw C., Hersh L.B. J. Biol. Chem. 264:6151-6157(1989) [PubMed: 2703483] [Abstract] Cited for: ACTIVE SITE ARG-103. |
| [4] | "Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity." Rougeot C., Messaoudi M., Hermitte V., Rigault A.G., Blisnick T., Dugave C., Desor D., Rougeon F. Proc. Natl. Acad. Sci. U.S.A. 100:8549-8554(2003) [PubMed: 12835417] [Abstract] Cited for: INHIBITION BY SIALORPHIN. |
Cross-references
Sequence databases | |
|---|---|
| M15944 mRNA. Translation: AAA41116.1. BC085753 mRNA. Translation: AAH85753.1. | |
| IPI | IPI00231789. |
| PIR | HYRTN. A29295. |
| RefSeq | NP_036740.1. |
| UniGene | Rn.33598 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1DMT based on UniProtKB P08473. |
| SMR | P07861. Positions 55-750. |
| ModBase | Search... |
Protein family/group databases | |
| MEROPS | M13.001. |
Proteomic databases | |
| PRIDE | P07861. |
Genome annotation databases | |
| Ensembl | ENSRNOG00000009514. Rattus norvegicus. [Contig view] |
| GeneID | 24590. |
| KEGG | rno:24590. |
Organism-specific databases | |
| RGD | 3098. Mme. |
Phylogenomic databases | |
| HOVERGEN | P07861. |
| OMA | P07861. GRNQIVF. |
Enzyme and pathway databases | |
| BRENDA | 3.4.24.11. 248. |
Gene expression databases | |
| ArrayExpress | P07861. |
| GermOnline | ENSRNOG00000009514. Rattus norvegicus. |
Family and domain databases | |
| InterPro | IPR006025. Pept_M_Zn_BS. IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view] |
| PANTHER | PTHR11733. Peptidase_M13. 1 hit. |
| Pfam | PF01431. Peptidase_M13. 1 hit. PF05649. Peptidase_M13_N. 1 hit. [Graphical view] |
| PRINTS | PR00786. NEPRILYSIN. |
| PROSITE | PS00142. ZINC_PROTEASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 603776. |
Entry information
| Entry name | NEP_RAT | ||||||||
| Accession | Primary (citable) accession number: P07861 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


