Protein: Membrane metallo-endopeptidase-like 1 (EC 3.4.24.11) (Membrane metallo-endopeptidase-like 2) (NEP2(m)) (Neprilysin II) (NEPII) (Neprilysin-2) (NEP2) (NL2) [Cleaved into: Membrane metallo-endopeptidase-like 1, soluble form (Neprilysin-2 secreted) (NEP2(s))] (Q495T6)
Organism: Homo sapiens (Human)
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).
Subcellular location: Membrane; Single-pass type II membrane protein. Secreted. Note=A secreted form produced by proteolytic cleavage also exists. {ECO:0000250}.
Sequence: MGKSEGPVGMVESAGRAGQKRPGFLEGGLLLLLLLVTAALVALGVLYADRRGKQLPRLASRLCFLQEERTFVKRKPRGIPEAQEVSEVCTTPGCVIAAARILQNMDPTTEPCDDFYQFACGGWLRRHVIPETNSRYSIFDVLRDELEVILKAVLENSTAKDRPAVEKARTLYRSCMNQSVIEKRGSQPLLDILEVVGGWPVAMDRWNETVGLEWELERQLALMNSQFNRRVLIDLFIWNDDQNSSRHIIYIDQPTLGMPSREYYFNGGSNRKVREAYLQFMVSVATLLREDANLPRDSCLVQEDMVQVLELETQLAKATVPQEERHDVIALYHRMGLEELQSQFGLKGFNWTLFIQTVLSSVKIKLLPDEEVVVYGIPYLQNLENIIDTYSARTIQNYLVWRLVLDRIGSLSQRFKDTRVNYRKALFGTMVEEVRWRECVGYVNSNMENAVGSLYVREAFPGDSKSMVRELIDKVRTVFVETLDELGWMDEESKKKAQEKAMSIREQIGHPDYILEEMNRRLDEEYSNLNFSEDLYFENSLQNLKVGAQRSLRKLREKVDPNLWIIGAAVVNAFYSPNRNQIVFPAGILQPPFFSKEQPQALNFGGIGMVIGHEITHGFDDNGRNFDKNGNMMDWWSNFSTQHFREQSECMIYQYGNYSWDLADEQNVNGFNTLGENIADNGGVRQAYKAYLKWMAEGGKDQQLPGLDLTHEQLFFINYAQVWCGSYRPEFAIQSIKTDVHSPLKYRVLGSLQNLAAFADTFHCARGTPMHPKERCRVW
InterPro domains: - IPR000718: Peptidase M13 (family) [33-779]
- IPR018497: Peptidase M13, C-terminal domain (domain) [564-778]
- IPR008753: Peptidase M13, N-terminal domain (domain) [111-511]
- IPR042089: Peptidase M13, domain 2 (homologous_superfamily) [137-559]
- IPR024079: Metallopeptidase, catalytic domain superfamily (homologous_superfamily) [89-779]
Interaction partners: - Insulin-degrading enzyme
- Amyloid-beta precursor protein
- Angiotensin-converting enzyme
- Beta-secretase 1
- Mineralocorticoid receptor
- Renin
- Presenilin-1
- Nicastrin
- Angiotensinogen
- Presenilin-2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0004175 (endopeptidase activity), GO:0008237 (metallopeptidase activity), GO:0004222 (metalloendopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0009628 (response to abiotic stimulus), GO:0048856 (anatomical structure development), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0006807 (nitrogen compound metabolic process), GO:0097242 (amyloid-beta clearance), GO:0042445 (hormone metabolic process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0003008 (system process), GO:0065008 (regulation of biological quality), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0044238 (primary metabolic process), GO:0009967 (positive regulation of signal transduction), GO:0001666 (response to hypoxia), GO:1901564 (organonitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0048731 (system development), GO:0070482 (response to oxygen levels), GO:0044057 (regulation of system process), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0008217 (regulation of blood pressure), GO:0042447 (hormone catabolic process), GO:0043170 (macromolecule metabolic process), GO:0003013 (circulatory system process), GO:0001921 (positive regulation of receptor recycling), GO:0010035 (response to inorganic substance), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0001919 (regulation of receptor recycling), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0043603 (amide metabolic process), GO:1901575 (organic substance catabolic process), GO:0090066 (regulation of anatomical structure size), GO:0010038 (response to metal ion), GO:0003018 (vascular process in circulatory system), GO:1901565 (organonitrogen compound catabolic process), GO:0006518 (peptide metabolic process), GO:0006508 (proteolysis), GO:0008015 (blood circulation), GO:0030163 (protein catabolic process), GO:0051604 (protein maturation), GO:0036293 (response to decreased oxygen levels), GO:0035150 (regulation of tube size), GO:0043171 (peptide catabolic process), GO:0036293 (response to decreased oxygen levels), GO:0003015 (heart process), GO:1902533 (positive regulation of intracellular signal transduction), GO:0010467 (gene expression), GO:1902531 (regulation of intracellular signal transduction), GO:0043408 (regulation of MAPK cascade), GO:0097746 (blood vessel diameter maintenance), GO:0035296 (regulation of tube diameter), GO:0043410 (positive regulation of MAPK cascade), GO:0016485 (protein processing), GO:0070372 (regulation of ERK1 and ERK2 cascade)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0005794 (Golgi apparatus), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0030667 (secretory granule membrane), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0031982 (vesicle), GO:0012506 (vesicle membrane), GO:0030659 (cytoplasmic vesicle membrane), GO:0000139 (Golgi membrane), GO:0097708 (intracellular vesicle)