NEUL_HUMAN
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 03-AUG-2022, entry version 170.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 46.
DR IntAct; Q9BYT8; 28.
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 BioMuta; NLN; -.
DR DMDM; 20139130; -.
DR EPD; Q9BYT8; -.
DR jPOST; Q9BYT8; -.
DR MassIVE; Q9BYT8; -.
DR MaxQB; Q9BYT8; -.
DR PaxDb; Q9BYT8; -.
DR PeptideAtlas; Q9BYT8; -.
DR PRIDE; Q9BYT8; -.
DR ProteomicsDB; 79707; -.
DR Antibodypedia; 23804; 282 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 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; KRSGAWC; -.
DR OrthoDB; 642479at2759; -.
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 1079 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 173 other tissues.
DR ExpressionAtlas; Q9BYT8; baseline and differential.
DR Genevisible; Q9BYT8; HS.
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 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 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
