ID   NEUL_PIG                Reviewed;         704 AA.
AC   Q02038; P79433; Q7JK54;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Neurolysin, mitochondrial;
DE            EC=3.4.24.16 {ECO:0000250|UniProtKB:P42676};
DE   AltName: Full=Endopeptidase 24.16;
DE   AltName: Full=Microsomal endopeptidase;
DE            Short=MEP;
DE   AltName: Full=Mitochondrial oligopeptidase M;
DE   AltName: Full=Neurotensin endopeptidase;
DE   AltName: Full=Soluble angiotensin-binding protein;
DE            Short=SABP;
DE   Flags: Precursor;
GN   Name=NLN;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE (ISOFORM 1),
RP   AND TISSUE SPECIFICITY.
RC   TISSUE=Heart, and Liver;
RX   PubMed=1517239; DOI=10.1016/s0021-9258(19)37153-4;
RA   Sugiura N., Hagiwara H., Hirose S.;
RT   "Molecular cloning of porcine soluble angiotensin-binding protein.";
RL   J. Biol. Chem. 267:18067-18072(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING (ISOFORMS 1;
RP   2; 3; 4 AND 5), AND SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=9182559; DOI=10.1074/jbc.272.24.15313;
RA   Kato A., Sugiura N., Saruta Y., Hosoiri T., Yasue H., Hirose S.;
RT   "Targeting of endopeptidase 24.16 to different subcellular compartments by
RT   alternative promoter usage.";
RL   J. Biol. Chem. 272:15313-15322(1997).
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: [Isoform 1]: Mitochondrion
CC       {ECO:0000269|PubMed:9182559}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC       {ECO:0000269|PubMed:9182559}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm
CC       {ECO:0000269|PubMed:9182559}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm
CC       {ECO:0000269|PubMed:9182559}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm
CC       {ECO:0000269|PubMed:9182559}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q02038-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q02038-2; Sequence=VSP_019392;
CC       Name=3; Synonyms=3';
CC         IsoId=Q02038-3; Sequence=VSP_019390;
CC       Name=4; Synonyms=1';
CC         IsoId=Q02038-4; Sequence=VSP_019393, VSP_019394;
CC       Name=5; Synonyms=2';
CC         IsoId=Q02038-5; Sequence=VSP_019391, VSP_019395;
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in the liver, kidney and
CC       adrenal gland. {ECO:0000269|PubMed:1517239}.
CC   -!- MISCELLANEOUS: [Isoform 4]: Truncated due to inclusion of exon 4 which
CC       leads to premature stop codon. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 5]: Truncated due to inclusion of exon 4 which
CC       leads to premature stop codon. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR   EMBL; D11336; BAA01949.1; -; mRNA.
DR   EMBL; AB000170; BAA19060.1; -; mRNA.
DR   EMBL; AB000170; BAA19061.1; -; mRNA.
DR   EMBL; AB000171; BAA19062.1; -; mRNA.
DR   EMBL; AB000172; BAA19063.1; -; mRNA.
DR   EMBL; AB000172; BAA19064.1; -; mRNA.
DR   EMBL; AB000173; BAA19065.1; -; mRNA.
DR   EMBL; AB000174; BAA19066.1; -; mRNA.
DR   EMBL; AB000175; BAA19067.1; -; mRNA.
DR   EMBL; AB000425; BAA19104.1; -; Genomic_DNA.
DR   EMBL; AB000425; BAA19105.1; -; Genomic_DNA.
DR   EMBL; AB000425; BAA19106.1; -; Genomic_DNA.
DR   PIR; A43411; A43411.
DR   RefSeq; NP_999524.1; NM_214359.2. [Q02038-1]
DR   RefSeq; XP_005654268.1; XM_005654211.2.
DR   RefSeq; XP_005654269.1; XM_005654212.2.
DR   RefSeq; XP_005672546.1; XM_005672489.2. [Q02038-3]
DR   RefSeq; XP_005672547.1; XM_005672490.2. [Q02038-3]
DR   RefSeq; XP_005672548.1; XM_005672491.2. [Q02038-3]
DR   RefSeq; XP_005672549.1; XM_005672492.2. [Q02038-3]
DR   AlphaFoldDB; Q02038; -.
DR   SMR; Q02038; -.
DR   STRING; 9823.ENSSSCP00000056095; -.
DR   MEROPS; M03.002; -.
DR   PaxDb; 9823-ENSSSCP00000017773; -.
DR   PeptideAtlas; Q02038; -.
DR   Ensembl; ENSSSCT00045059491.1; ENSSSCP00045041710.1; ENSSSCG00045031968.1. [Q02038-3]
DR   Ensembl; ENSSSCT00045059584.1; ENSSSCP00045041791.1; ENSSSCG00045031968.1. [Q02038-1]
DR   Ensembl; ENSSSCT00045059900.1; ENSSSCP00045042044.1; ENSSSCG00045031968.1. [Q02038-3]
DR   Ensembl; ENSSSCT00045059985.1; ENSSSCP00045042112.1; ENSSSCG00045031968.1. [Q02038-3]
DR   Ensembl; ENSSSCT00055039328.1; ENSSSCP00055031280.1; ENSSSCG00055017425.1. [Q02038-1]
DR   Ensembl; ENSSSCT00055039770.1; ENSSSCP00055031634.1; ENSSSCG00055017425.1. [Q02038-3]
DR   Ensembl; ENSSSCT00065039587.1; ENSSSCP00065016753.1; ENSSSCG00065029069.1. [Q02038-3]
DR   Ensembl; ENSSSCT00065039591.1; ENSSSCP00065016755.1; ENSSSCG00065029069.1. [Q02038-1]
DR   Ensembl; ENSSSCT00065039602.1; ENSSSCP00065016762.1; ENSSSCG00065029069.1. [Q02038-3]
DR   Ensembl; ENSSSCT00065039610.1; ENSSSCP00065016765.1; ENSSSCG00065029069.1. [Q02038-3]
DR   GeneID; 397646; -.
DR   KEGG; ssc:397646; -.
DR   CTD; 57486; -.
DR   eggNOG; KOG2089; Eukaryota.
DR   HOGENOM; CLU_001805_2_0_1; -.
DR   InParanoid; Q02038; -.
DR   OMA; RSGAWCS; -.
DR   OrthoDB; 735202at2759; -.
DR   BRENDA; 3.4.24.16; 6170.
DR   Reactome; R-SSC-375276; Peptide ligand-binding receptors.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   Bgee; ENSSSCG00000016778; Expressed in adult mammalian kidney and 46 other cell types or tissues.
DR   ExpressionAtlas; Q02038; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; TAS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   CDD; cd06455; M3A_TOP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 1.10.1370.10; Neurolysin, domain 3; 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:SF44; NEUROLYSIN, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR11804; PROTEASE M3 THIMET OLIGOPEPTIDASE-RELATED; 1.
DR   Pfam; PF01432; Peptidase_M3; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; Q02038; SS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW   Hydrolase; 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_0000028576"
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"
FT   VAR_SEQ         1..136
FT                   /note="MIVRCLSAARRLHRVGGSGILLRMTLGREAMSPLQAMSSYTVDGRNVLRWDL
FT                   SPEQIKRRTEELIAQTKQVYDDIGMLDIEEVTYENCLQALADVEVKYIVERTMLDFPQH
FT                   VSSDKEVRAASTEADKRLSRFDIEM -> MVYPEGHLARELGATFSSSAPLGGHPFPFV
FT                   WDCLSCKQGDWSQARPKTNAERRSGETPLSKFHILALVPLSILPVPRQKPGCHPESLTS
FT                   STHLGWWFRDFIENDFRERSNVSSSGNVFLYCGWQKCFKMGSFTRAN (in isoform
FT                   5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019391"
FT   VAR_SEQ         1..23
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019390"
FT   VAR_SEQ         1..14
FT                   /note="MIVRCLSAARRLHR -> MVYPEGHLARELGATFSSSAPLGGHPFPFVWDCL
FT                   SCKQGDWSQARPKTNAERRSG (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019392"
FT   VAR_SEQ         15..95
FT                   /note="VGGSGILLRMTLGREAMSPLQAMSSYTVDGRNVLRWDLSPEQIKRRTEELIA
FT                   QTKQVYDDIGMLDIEEVTYENCLQALADV -> ETPLSKFHILALVPLSILPVPRQKPG
FT                   CHPESLTSSTHLGWWFRDFIENDFRERSNVSSSGNVFLYCGWQKCFKMGSFTRAN (in
FT                   isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019393"
FT   VAR_SEQ         96..704
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019394"
FT   VAR_SEQ         137..704
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_019395"
SQ   SEQUENCE   704 AA;  80757 MW;  A02BFEC67B7044A1 CRC64;
     MIVRCLSAAR RLHRVGGSGI LLRMTLGREA MSPLQAMSSY TVDGRNVLRW DLSPEQIKRR
     TEELIAQTKQ VYDDIGMLDI EEVTYENCLQ ALADVEVKYI VERTMLDFPQ HVSSDKEVRA
     ASTEADKRLS RFDIEMSMRE DIFLRIVRLK ETCDLGKIKP EARRYLEKSV KMGKRNGLHL
     PEQVQNEIKA MKKRMSELCI DFNKNLNEDD TFLVFSKAEL GALPDDFIDS LEKTDDNKYK
     ITLKYPHYFP VMKKCCIPET RRKMEMAFNT RCKEENTIIL QELLPLRAKV AKLLGYSTHA
     DFVLEMNTAK STHHVTAFLD DLSQKLKPLG EAEREFILNL KKKECEEKGF EYDGKINAWD
     LHYYMTQTEE LKYSVDQEIL KEYFPIEVVT EGLLNIYQEL LGLSFEQVTD AHVWNKSVTL
     YTVKDKATGE VLGQFYLDLY PREGKYNHAA CFGLQPGCLL PDGSRMMSVA ALVVNFSQPR
     AGRPSLLRHD EVRTYFHEFG HVMHQICAQT DFARFSGTNV ETDFVEVPSQ MLENWVWDTD
     SLRRLSKHYK DGSPITDDLL EKLVASRLVN TGLLTLRQIV LSKVDQSLHT NTSLDAASEY
     AKYCTEILGV AATPGTNMPA TFGHLAGGYD GQYYGYLWSE VFSMDMFYSC FKKEGIMNPE
     VGMKYRNLIL KPGGSLDGMD MLQNFLKREP NQKAFLMSRG LHAP
//