ID   NEUL_HUMAN              Reviewed;         704 AA.
AC   Q9BYT8; Q9ULJ4;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Neurolysin, mitochondrial;
DE            EC=3.4.24.16 {ECO:0000250|UniProtKB:P42676};
DE   AltName: Full=Angiotensin-binding protein;
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; Synonyms=AGTBP, KIAA1226;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Chen J.M., Rawlings N.D., Barrett A.J.;
RT   "Cloning and sequencing of human neurolysin, an oligopeptidase of family
RT   M3.";
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA   Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:337-345(1999).
RN   [3]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-664, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
CC   -!- FUNCTION: Hydrolyzes oligopeptides such as neurotensin, bradykinin and
CC       dynorphin A (By similarity). Acts as a regulator of cannabinoid
CC       signaling pathway by mediating degradation of hemopressin, an
CC       antagonist peptide of the cannabinoid receptor CNR1 (By similarity).
CC       {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; AJ300837; CAC27329.1; -; mRNA.
DR   EMBL; AB033052; BAA86540.2; -; mRNA.
DR   CCDS; CCDS3989.1; -.
DR   RefSeq; NP_065777.1; NM_020726.4.
DR   PDB; 5LUZ; X-ray; 2.70 A; A/B=38-704.
DR   PDB; 5LV0; X-ray; 2.70 A; A/B=38-704.
DR   PDBsum; 5LUZ; -.
DR   PDBsum; 5LV0; -.
DR   AlphaFoldDB; Q9BYT8; -.
DR   SMR; Q9BYT8; -.
DR   BioGRID; 121555; 60.
DR   IntAct; Q9BYT8; 29.
DR   STRING; 9606.ENSP00000370372; -.
DR   MEROPS; M03.002; -.
DR   GlyGen; Q9BYT8; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9BYT8; -.
DR   PhosphoSitePlus; Q9BYT8; -.
DR   SwissPalm; Q9BYT8; -.
DR   BioMuta; NLN; -.
DR   DMDM; 20139130; -.
DR   EPD; Q9BYT8; -.
DR   jPOST; Q9BYT8; -.
DR   MassIVE; Q9BYT8; -.
DR   MaxQB; Q9BYT8; -.
DR   PaxDb; 9606-ENSP00000370372; -.
DR   PeptideAtlas; Q9BYT8; -.
DR   ProteomicsDB; 79707; -.
DR   Pumba; Q9BYT8; -.
DR   Antibodypedia; 23804; 328 antibodies from 26 providers.
DR   DNASU; 57486; -.
DR   Ensembl; ENST00000380985.10; ENSP00000370372.5; ENSG00000123213.23.
DR   GeneID; 57486; -.
DR   KEGG; hsa:57486; -.
DR   MANE-Select; ENST00000380985.10; ENSP00000370372.5; NM_020726.5; NP_065777.1.
DR   UCSC; uc003juf.3; human.
DR   AGR; HGNC:16058; -.
DR   CTD; 57486; -.
DR   DisGeNET; 57486; -.
DR   GeneCards; NLN; -.
DR   HGNC; HGNC:16058; NLN.
DR   HPA; ENSG00000123213; Low tissue specificity.
DR   MIM; 611530; gene.
DR   neXtProt; NX_Q9BYT8; -.
DR   OpenTargets; ENSG00000123213; -.
DR   PharmGKB; PA31651; -.
DR   VEuPathDB; HostDB:ENSG00000123213; -.
DR   eggNOG; KOG2089; Eukaryota.
DR   GeneTree; ENSGT00950000183171; -.
DR   InParanoid; Q9BYT8; -.
DR   OMA; RSGAWCS; -.
DR   OrthoDB; 735202at2759; -.
DR   PhylomeDB; Q9BYT8; -.
DR   TreeFam; TF300459; -.
DR   BRENDA; 3.4.24.16; 2681.
DR   PathwayCommons; Q9BYT8; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   SignaLink; Q9BYT8; -.
DR   BioGRID-ORCS; 57486; 13 hits in 1158 CRISPR screens.
DR   ChiTaRS; NLN; human.
DR   GeneWiki; NLN_(gene); -.
DR   GenomeRNAi; 57486; -.
DR   Pharos; Q9BYT8; Tbio.
DR   PRO; PR:Q9BYT8; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9BYT8; Protein.
DR   Bgee; ENSG00000123213; Expressed in endothelial cell and 174 other cell types or tissues.
DR   ExpressionAtlas; Q9BYT8; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl.
DR   GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; IEA:Ensembl.
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; Q9BYT8; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Hydrolase; Metal-binding;
KW   Metalloprotease; Mitochondrion; Protease; Reference proteome;
KW   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_0000028575"
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:0007744|PubMed:19608861"
FT   VARIANT         79
FT                   /note="G -> S (in dbSNP:rs34339013)"
FT                   /id="VAR_062224"
FT   VARIANT         323
FT                   /note="S -> G (in dbSNP:rs34063558)"
FT                   /id="VAR_054002"
FT   VARIANT         372
FT                   /note="K -> R (in dbSNP:rs6863012)"
FT                   /id="VAR_054003"
FT   VARIANT         417
FT                   /note="S -> G (in dbSNP:rs2289884)"
FT                   /id="VAR_054004"
FT   VARIANT         704
FT                   /note="P -> S (in dbSNP:rs6860508)"
FT                   /id="VAR_024594"
FT   HELIX           54..77
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            80..82
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            85..88
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           89..107
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           109..112
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           116..137
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           140..152
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           155..157
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           160..175
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            176..179
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           182..208
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          212..215
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            217..222
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          229..231
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          239..244
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           245..254
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           258..268
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            269..272
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           273..293
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           299..304
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           312..348
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            358..360
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           361..373
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           377..380
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           381..383
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           386..401
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          404..408
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          419..424
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          426..428
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          431..438
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          450..455
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          461..465
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          468..473
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           489..507
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           513..515
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            522..526
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           527..532
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           533..536
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           539..545
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            549..551
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           557..565
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           566..568
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           571..588
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   STRAND          592..594
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           596..606
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           619..621
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           623..625
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            626..628
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           635..649
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            650..653
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           659..669
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   TURN            670..672
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           673..675
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           678..686
FT                   /evidence="ECO:0007829|PDB:5LUZ"
FT   HELIX           693..699
FT                   /evidence="ECO:0007829|PDB:5LUZ"
SQ   SEQUENCE   704 AA;  80652 MW;  80136688D79BBEDF CRC64;
     MIARCLLAVR SLRRVGGSRI LLRMTLGREV MSPLQAMSSY TVAGRNVLRW DLSPEQIKTR
     TEELIVQTKQ VYDAVGMLGI EEVTYENCLQ ALADVEVKYI VERTMLDFPQ HVSSDKEVRA
     ASTEADKRLS RFDIEMSMRG DIFERIVHLQ ETCDLGKIKP EARRYLEKSI KMGKRNGLHL
     PEQVQNEIKS MKKRMSELCI DFNKNLNEDD TFLVFSKAEL GALPDDFIDS LEKTDDDKYK
     ITLKYPHYFP VMKKCCIPET RRRMEMAFNT RCKEENTIIL QQLLPLRTKV AKLLGYSTHA
     DFVLEMNTAK STSRVTAFLD DLSQKLKPLG EAEREFILNL KKKECKDRGF EYDGKINAWD
     LYYYMTQTEE LKYSIDQEFL KEYFPIEVVT EGLLNTYQEL LGLSFEQMTD AHVWNKSVTL
     YTVKDKATGE VLGQFYLDLY PREGKYNHAA CFGLQPGCLL PDGSRMMAVA ALVVNFSQPV
     AGRPSLLRHD EVRTYFHEFG HVMHQICAQT DFARFSGTNV ETDFVEVPSQ MLENWVWDVD
     SLRRLSKHYK DGSPIADDLL EKLVASRLVN TGLLTLRQIV LSKVDQSLHT NTSLDAASEY
     AKYCSEILGV AATPGTNMPA TFGHLAGGYD GQYYGYLWSE VFSMDMFYSC FKKEGIMNPE
     VGMKYRNLIL KPGGSLDGMD MLHNFLKREP NQKAFLMSRG LHAP
//