NEUL_PIG
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 03-AUG-2022, entry version 139.
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.ENSSSCP00000017773; -.
DR MEROPS; M03.002; -.
DR PaxDb; Q02038; -.
DR PeptideAtlas; Q02038; -.
DR PRIDE; Q02038; -.
DR Ensembl; ENSSSCT00000018459; ENSSSCP00000017959; ENSSSCG00000016778. [Q02038-3]
DR Ensembl; ENSSSCT00045059491; ENSSSCP00045041710; ENSSSCG00045031968. [Q02038-3]
DR Ensembl; ENSSSCT00045059584; ENSSSCP00045041791; ENSSSCG00045031968. [Q02038-1]
DR Ensembl; ENSSSCT00045059900; ENSSSCP00045042044; ENSSSCG00045031968. [Q02038-3]
DR Ensembl; ENSSSCT00045059985; ENSSSCP00045042112; ENSSSCG00045031968. [Q02038-3]
DR Ensembl; ENSSSCT00055039328; ENSSSCP00055031280; ENSSSCG00055017425. [Q02038-1]
DR Ensembl; ENSSSCT00055039770; ENSSSCP00055031634; ENSSSCG00055017425. [Q02038-3]
DR Ensembl; ENSSSCT00065039587; ENSSSCP00065016753; ENSSSCG00065029069. [Q02038-3]
DR Ensembl; ENSSSCT00065039591; ENSSSCP00065016755; ENSSSCG00065029069. [Q02038-1]
DR Ensembl; ENSSSCT00065039602; ENSSSCP00065016762; ENSSSCG00065029069. [Q02038-3]
DR Ensembl; ENSSSCT00065039610; ENSSSCP00065016765; ENSSSCG00065029069. [Q02038-3]
DR GeneID; 397646; -.
DR KEGG; ssc:397646; -.
DR CTD; 57486; -.
DR eggNOG; KOG2089; Eukaryota.
DR GeneTree; ENSGT00950000183171; -.
DR HOGENOM; CLU_001805_2_0_1; -.
DR InParanoid; Q02038; -.
DR OMA; KRSGAWC; -.
DR BRENDA; 3.4.24.16; 6170.
DR Reactome; R-SSC-375276; Peptide ligand-binding receptors.
DR Proteomes; UP000008227; Chromosome 16.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000016778; Expressed in adult mammalian kidney and 46 other tissues.
DR ExpressionAtlas; Q02038; baseline and differential.
DR Genevisible; Q02038; SS.
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 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; 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
