ID   NEUL_RABIT              Reviewed;         704 AA.
AC   P42675;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Neurolysin, mitochondrial;
DE            EC=3.4.24.16 {ECO:0000250|UniProtKB:P42676};
DE   AltName: Full=Microsomal endopeptidase;
DE            Short=MEP;
DE   AltName: Full=Mitochondrial oligopeptidase M;
DE   AltName: Full=Neurotensin endopeptidase;
DE   Flags: Precursor;
GN   Name=NLN;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Liver;
RX   PubMed=8509389; DOI=10.1016/s0021-9258(18)31416-9;
RA   Kawabata S., Nakagawa K., Muta T., Iwanaga S., Davie E.W.;
RT   "Rabbit liver microsomal endopeptidase with substrate specificity for
RT   processing proproteins is structurally related to rat testes
RT   metalloendopeptidase 24.15.";
RL   J. Biol. Chem. 268:12498-12503(1993).
CC   -!- FUNCTION: Hydrolyzes oligopeptides such as neurotensin, bradykinin and
CC       dynorphin A. Acts as a regulator of cannabinoid signaling pathway by
CC       mediating degradation of hemopressin, an antagonist peptide of the
CC       cannabinoid receptor CNR1. {ECO:0000250|UniProtKB:P42676}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage in neurotensin: 10-Pro-|-Tyr-11.;
CC         EC=3.4.24.16; Evidence={ECO:0000250|UniProtKB:P42676};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P52888};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P52888};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC       {ECO:0000250|UniProtKB:P42676}. Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P42676}.
CC   -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR   EMBL; D13310; BAA02570.1; -; mRNA.
DR   PIR; A45985; A45985.
DR   RefSeq; XP_008260508.1; XM_008262286.1.
DR   AlphaFoldDB; P42675; -.
DR   SMR; P42675; -.
DR   STRING; 9986.ENSOCUP00000008123; -.
DR   MEROPS; M03.002; -.
DR   Ensembl; ENSOCUT00000048278; ENSOCUP00000044032; ENSOCUG00000009420.
DR   GeneID; 100357326; -.
DR   KEGG; ocu:100357326; -.
DR   CTD; 57486; -.
DR   eggNOG; KOG2089; Eukaryota.
DR   GeneTree; ENSGT00950000183171; -.
DR   InParanoid; P42675; -.
DR   OrthoDB; 642479at2759; -.
DR   Proteomes; UP000001811; Chromosome 11.
DR   Bgee; ENSOCUG00000009420; Expressed in heart and 14 other tissues.
DR   ExpressionAtlas; P42675; baseline.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1370.10; -; 1.
DR   Gene3D; 1.20.1050.40; -; 1.
DR   Gene3D; 3.40.390.10; -; 1.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR024077; Neurolysin/TOP_dom2.
DR   InterPro; IPR024080; Neurolysin/TOP_N.
DR   InterPro; IPR045090; Pept_M3A_M3B.
DR   InterPro; IPR001567; Pept_M3A_M3B_dom.
DR   PANTHER; PTHR11804; PTHR11804; 1.
DR   Pfam; PF01432; Peptidase_M3; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase;
KW   Metal-binding; Metalloprotease; Mitochondrion; Protease;
KW   Reference proteome; Transit peptide; Zinc.
FT   TRANSIT         1..37
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P42676"
FT   CHAIN           38..704
FT                   /note="Neurolysin, mitochondrial"
FT                   /id="PRO_0000028577"
FT   ACT_SITE        498
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         497
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         501
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         504
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   MOD_RES         664
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYT8"
SQ   SEQUENCE   704 AA;  80689 MW;  A1B7E4DE38E8088C CRC64;
     MIARCFSAVR GLHRVGGSRI LFKMTLGREV MSPLQAVSSY TAAGRNVLRW DLSPEQIKTR
     TEELIAQTKQ VYDSVGMLDI KDVTYENCLQ ALADVEVKYI VERTMLDFPQ HVSTDREVRA
     ASTEADKRLS RFDIEMSMRE DIFQRIVHLQ ETCDLEKIKP EARRYLEKSV KMGRRNGLHL
     PEEVQNEIKS MKKRMSELCI DFNKNLNEDD TFLVFSKAEL GALPDDFIDS LEKMDDDKYK
     ITLKYPHYFP VMKKCCIPET RRRMEMAFNT RCKEENTVIL QQLLPLRAQV AKLLGYSTHA
     DFVLEMNTAK STSRVTAFLD DLSQKLKPLG EAEREFILSL KKKECEEKGF EYDGKINAWD
     LHYYMTQTEE LKYSIDQEFI KEYFPIEVVT EGLLNIYQEL LGLSFEQVAD AHVWNPSVTL
     YTVKDKATGE VLGQFYLDLY PREGKYNHAA CFGLQPGCLL PDGSRMLSVA ALVVNFSQPV
     AGRPSLLRHD EVRTYFHEFG HVMHQICAQT DFARFSGTNV ETDFVEVPSQ MLENWVWDID
     SLRRLSKHYK DGNPIADDLL EKLVASRLVN TGLLTLRQIV LSKVDQSLHT NSSLDAASEY
     ARYCTDILGV AATPGTNMPA TFGHLAGGYD GQYYGYLWSE VFSMDMFYSC FKKEGIMNPE
     VGMKYRNLIL RPGGSLDGMD MLQNFLQREP NQKAFLMSRG LQAP