| IED ID | IndEnz0002004147 |
| Enzyme Type ID | protease004147 |
| Protein Name |
Membrane metallo-endopeptidase-like 1 EC 3.4.24.11 NEP2 m Neprilysin II NEPII Neprilysin-2 NEP2 NL2 Cleaved into: Membrane metallo-endopeptidase-like 1, soluble form Neprilysin-2 secreted NEP2 s |
| Gene Name | Mmel1 Mell1 Nep2 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MGKSESSVGMMERADNCGRRRLGFVECGLLVLLTLLLMGAIVTLGVFYSIGKQLPLLNSLLHVSRHERTVVKRVLRDSSQKSDICTTPSCVIAAARILQNMDQSKKPCDNFYQYACGGWLRHHVIPETNSRYSVFDILRDELEVILKGVLEDSSVQHRPAVEKAKTLYRSCMNQSVIEKRDSEPLLNVLDMIGGWPVAMDKWNETMGPKWELERQLAVLNSQFNRRVLIDLFIWNDDQNSSRHVIYIDQPTLGMPSREYYFKEDSHRVREAYLQFMTSVATMLRRDLNLPGETDLVQEEMAQVLHLETHLANATVPQEKRHDVTALYHRMGLEELQERFGLKGFNWTLFIQNVLSSVQVELLPNEEVVVYGIPYLENLEEIIDVFPAQTLQNYLVWRLVLDRIGSLSQRFKEARVDYRKALYGTTMEEVRWRECVSYVNSNMESAVGSLYIKRAFSKDSKSIVSELIEKIRSVFVDNLDELNWMDEESKKKAQEKALNIREQIGYPDYILEDNNRHLDEEYSSLTFSEDLYFENGLQNLKNNAQRSLKKLREKVDQNLWIIGAAVVNAFYSPNRNLIVFPAGILQPPFFSKDQPQALNFGGIGMVIGHEITHGFDDNGRNFDKNGNMLDWWSNFSARHFRQQSQCMIYQYSNFSWELADNQNVNGFSTLGENIADNGGVRQAYKAYLQWLAEGGRDQRLPGLNLTYAQLFFINYAQVWCGSYRPEFAIQSIKTDVHSPLNAQVLGSLQNLPGFSEAFHCPRGSPMHPMNRCRIW |
| Enzyme Length | 774 |
| Uniprot Accession Number | P0C1T0 |
| Absorption | |
| Active Site | ACT_SITE 609; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; ACT_SITE 675; /note="Proton donor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by thiorphan and phosphoramidon. |
| Binding Site | BINDING 131; /note=Substrate carboxyl; /evidence=ECO:0000305 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11; |
| DNA Binding | |
| EC Number | 3.4.24.11 |
| Enzyme Function | FUNCTION: Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond (By similarity). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (3); Binding site (1); Chain (2); Coiled coil (1); Disulfide bond (5); Domain (1); Glycosylation (8); Metal binding (3); Motif (1); Mutagenesis (7); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Coiled coil;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal-anchor;Transmembrane;Transmembrane helix;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein. Secreted. Note=A secreted form produced by proteolytic cleavage also exists. {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated. {ECO:0000269|PubMed:11964170}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 14..21; /note=Stop-transfer sequence; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 89,197 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=62 uM for Tyrosyl-D-Ala(2)-Leu(5)-enkephalin {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=27 uM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=50 uM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1, soluble form) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=40 uM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=100 uM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1, soluble form) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=23 uM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; KM=35 uM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1, soluble form) {ECO:0000269|PubMed:11964170, ECO:0000269|PubMed:15294904}; |
| Metal Binding | METAL 608; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 612; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 671; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.B14; |