NEUL_RAT
ID NEUL_RAT Reviewed; 704 AA.
AC P42676; Q6GQQ4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Neurolysin, mitochondrial;
DE EC=3.4.24.16 {ECO:0000269|PubMed:12500972, ECO:0000269|PubMed:7836437};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7592986; DOI=10.1074/jbc.270.45.27266;
RA Dauch P., Vincent J.-P., Checler F.;
RT "Molecular cloning and expression of rat brain endopeptidase 3.4.24.16.";
RL J. Biol. Chem. 270:27266-27271(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 38-57, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Liver;
RX PubMed=7836437; DOI=10.1074/jbc.270.5.2092;
RA Serizawa A., Dando P.M., Barrett A.J.;
RT "Characterization of a mitochondrial metallopeptidase reveals neurolysin as
RT a homologue of thimet oligopeptidase.";
RL J. Biol. Chem. 270:2092-2098(1995).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=11248043; DOI=10.1073/pnas.051633198;
RA Brown C.K., Madauss K., Lian W., Beck M.R., Tolbert W.D., Rodgers D.W.;
RT "Structure of neurolysin reveals a deep channel that limits substrate
RT access.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3127-3132(2001).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12500972; DOI=10.1074/jbc.m212030200;
RA Rioli V., Gozzo F.C., Heimann A.S., Linardi A., Krieger J.E., Shida C.S.,
RA Almeida P.C., Hyslop S., Eberlin M.N., Ferro E.S.;
RT "Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and
RT angiotensin-converting enzyme.";
RL J. Biol. Chem. 278:8547-8555(2003).
RN [6]
RP FUNCTION.
RX PubMed=18077343; DOI=10.1073/pnas.0706980105;
RA Heimann A.S., Gomes I., Dale C.S., Pagano R.L., Gupta A., de Souza L.L.,
RA Luchessi A.D., Castro L.M., Giorgi R., Rioli V., Ferro E.S., Devi L.A.;
RT "Hemopressin is an inverse agonist of CB1 cannabinoid receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20588-20593(2007).
CC -!- FUNCTION: Hydrolyzes oligopeptides such as neurotensin, bradykinin and
CC dynorphin A (PubMed:7836437). Acts as a regulator of cannabinoid
CC signaling pathway by mediating degradation of hemopressin, an
CC antagonist peptide of the cannabinoid receptor CNR1 (PubMed:12500972,
CC PubMed:18077343). {ECO:0000269|PubMed:12500972,
CC ECO:0000269|PubMed:18077343, ECO:0000269|PubMed:7836437}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage in neurotensin: 10-Pro-|-Tyr-11.;
CC EC=3.4.24.16; Evidence={ECO:0000269|PubMed:12500972,
CC ECO:0000269|PubMed:7836437};
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:0000269|PubMed:7836437}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:7836437}.
CC -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR EMBL; X87157; CAA60630.1; -; mRNA.
DR EMBL; BC072687; AAH72687.1; -; mRNA.
DR RefSeq; NP_446422.2; NM_053970.2.
DR PDB; 1I1I; X-ray; 2.30 A; P=24-704.
DR PDB; 2O3E; X-ray; 2.20 A; A=24-701.
DR PDB; 4FXY; X-ray; 2.80 A; P/Q=24-704.
DR PDBsum; 1I1I; -.
DR PDBsum; 2O3E; -.
DR PDBsum; 4FXY; -.
DR AlphaFoldDB; P42676; -.
DR SMR; P42676; -.
DR STRING; 10116.ENSRNOP00000059652; -.
DR MEROPS; M03.002; -.
DR iPTMnet; P42676; -.
DR PhosphoSitePlus; P42676; -.
DR SwissPalm; P42676; -.
DR jPOST; P42676; -.
DR PaxDb; P42676; -.
DR PRIDE; P42676; -.
DR GeneID; 117041; -.
DR KEGG; rno:117041; -.
DR UCSC; RGD:621518; rat.
DR CTD; 57486; -.
DR RGD; 621518; Nln.
DR eggNOG; KOG2089; Eukaryota.
DR InParanoid; P42676; -.
DR OrthoDB; 642479at2759; -.
DR PhylomeDB; P42676; -.
DR TreeFam; TF300459; -.
DR BRENDA; 3.4.24.16; 5301.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR EvolutionaryTrace; P42676; -.
DR PRO; PR:P42676; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:RGD.
DR GO; GO:0070012; F:oligopeptidase activity; IDA:RGD.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; ISO:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA:UniProtKB.
DR GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISO:RGD.
DR GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; ISO:RGD.
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; 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:0000269|PubMed:7836437"
FT CHAIN 38..704
FT /note="Neurolysin, mitochondrial"
FT /id="PRO_0000028578"
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 CONFLICT 128
FT /note="K -> R (in Ref. 2; AAH72687)"
FT /evidence="ECO:0000305"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 54..75
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 85..88
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 89..107
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 116..137
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 160..175
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 176..179
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 182..187
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 189..208
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 217..222
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 225..229
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:4FXY"
FT STRAND 235..244
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 245..254
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 258..268
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 269..272
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 273..293
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 299..304
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 312..347
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 377..380
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 386..401
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 403..407
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 419..425
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 426..428
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 431..438
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 468..473
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:4FXY"
FT HELIX 489..507
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 522..526
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 527..533
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 534..537
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 539..545
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 557..565
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 566..570
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 571..588
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 596..606
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 618..621
FT /evidence="ECO:0007829|PDB:2O3E"
FT STRAND 625..628
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 635..649
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 651..654
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 659..669
FT /evidence="ECO:0007829|PDB:2O3E"
FT TURN 670..672
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 678..686
FT /evidence="ECO:0007829|PDB:2O3E"
FT HELIX 693..699
FT /evidence="ECO:0007829|PDB:2O3E"
SQ SEQUENCE 704 AA; 80254 MW; E33F7967A79343D1 CRC64;
MITLCLSTLR GLHRAGGSRL QLTMTLGKEL ASPLQAMSSY TAAGRNVLRW DLSPEQIKTR
TEQLIAQTKQ VYDTVGTIAL KEVTYENCLQ VLADIEVTYI VERTMLDFPQ HVSSDREVRA
ASTEADKKLS RFDIEMSMRE DVFQRIVHLQ ETCDLEKIKP EARRYLEKSI KMGKRNGLHL
SEHIRNEIKS MKKRMSELCI DFNKNLNEDD TSLVFSKAEL GALPDDFIDS LEKTDEDKYK
VTLKYPHYFP VMKKCCVPET RRKMEMAFHT RCKQENTAIL QQLLPLRAQV AKLLGYNTHA
DFVLELNTAK STSRVAAFLD DLSQKLKPLG EAEREFILSL KKKECEERGF EYDGKINAWD
LHYYMTQTEE LKYSVDQESL KEYFPIEVVT EGLLSIYQEL LGLSFEQVPD AHVWNKSVSL
YTVKDKATGE VLGQFYLDLY PREGKYNHAA CFGLQPGCLL PDGSRMMSVA ALVVNFSQPV
AGRPSLLRHD EVRTYFHEFG HVMHQICAQT DFARFSGTNV ETDFVEVPSQ MLENWVWDVD
SLRKLSKHYK DGHPITDELL EKLVASRLVN TGLLTLRQIV LSKVDQSLHT NATLDAASEY
AKYCTEILGV AATPGTNMPA TFGHLAGGYD GQYYGYLWSE VFSMDMFHSC FKKEGIMNPE
VGMKYRNLIL KPGGSLDGMD MLQNFLQREP NQKAFLMSRG LNGS
