ID   NEUL_MOUSE              Reviewed;         704 AA.
AC   Q91YP2; Q3UJP1; Q8R3F4;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 152.
DE   RecName: Full=Neurolysin, mitochondrial;
DE            EC=3.4.24.16 {ECO:0000250|UniProtKB:P42676};
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Diencephalon;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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: 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; AK079090; BAC37533.1; -; mRNA.
DR   EMBL; AK146364; BAE27114.1; -; mRNA.
DR   EMBL; BC016224; AAH16224.1; -; mRNA.
DR   EMBL; BC025520; AAH25520.1; -; mRNA.
DR   CCDS; CCDS36772.1; -.
DR   RefSeq; NP_083723.1; NM_029447.2.
DR   AlphaFoldDB; Q91YP2; -.
DR   SMR; Q91YP2; -.
DR   STRING; 10090.ENSMUSP00000104938; -.
DR   MEROPS; M03.002; -.
DR   iPTMnet; Q91YP2; -.
DR   PhosphoSitePlus; Q91YP2; -.
DR   SwissPalm; Q91YP2; -.
DR   EPD; Q91YP2; -.
DR   MaxQB; Q91YP2; -.
DR   PaxDb; 10090-ENSMUSP00000104938; -.
DR   PeptideAtlas; Q91YP2; -.
DR   ProteomicsDB; 252952; -.
DR   Pumba; Q91YP2; -.
DR   Antibodypedia; 23804; 328 antibodies from 26 providers.
DR   DNASU; 75805; -.
DR   Ensembl; ENSMUST00000109315.5; ENSMUSP00000104938.4; ENSMUSG00000021710.12.
DR   GeneID; 75805; -.
DR   KEGG; mmu:75805; -.
DR   UCSC; uc007rsp.1; mouse.
DR   AGR; MGI:1923055; -.
DR   CTD; 57486; -.
DR   MGI; MGI:1923055; Nln.
DR   VEuPathDB; HostDB:ENSMUSG00000021710; -.
DR   eggNOG; KOG2089; Eukaryota.
DR   GeneTree; ENSGT00950000183171; -.
DR   HOGENOM; CLU_001805_2_0_1; -.
DR   InParanoid; Q91YP2; -.
DR   OMA; RSGAWCS; -.
DR   OrthoDB; 735202at2759; -.
DR   PhylomeDB; Q91YP2; -.
DR   TreeFam; TF300459; -.
DR   BRENDA; 3.4.24.16; 3474.
DR   Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR   BioGRID-ORCS; 75805; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Nln; mouse.
DR   PRO; PR:Q91YP2; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q91YP2; Protein.
DR   Bgee; ENSMUSG00000021710; Expressed in embryonic post-anal tail and 248 other cell types or tissues.
DR   ExpressionAtlas; Q91YP2; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISO:MGI.
DR   GO; GO:0070012; F:oligopeptidase activity; ISO:MGI.
DR   GO; GO:0008233; F:peptidase activity; IMP:MGI.
DR   GO; GO:0042277; F:peptide binding; IPI:MGI.
DR   GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR   GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR   GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0006111; P:regulation of gluconeogenesis; IMP:MGI.
DR   GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; IMP:MGI.
DR   CDD; cd09605; M3A; 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; Q91YP2; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Hydrolase; Metal-binding; Metalloprotease;
KW   Mitochondrion; Protease; 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_0000319046"
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        44
FT                   /note="G -> V (in Ref. 1; BAE27114)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        329..331
FT                   /note="LGE -> HAS (in Ref. 2; AAH25520)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   704 AA;  80429 MW;  E4F342E346AB0E07 CRC64;
     MITLCLSALR GLHRAGGSRI RLRMTLGREA ASPLQAMSSY TAAGRNVLRW DLSPEQIRTR
     TEELIAQTKQ VYDTVGTINL EDVTYENCLQ VLADIEVKYI VERTMLDFPQ HVSSDREVRA
     ASTEADKRLS RFDIEMSMRE DVFQRIVHLQ ETCDLEKIKP EARRYLEKSI KMGKRNGLHL
     PEHVKNEIKS MKKRMSELCI DFNKNLNEDD TSLVFSKAEL GALPDDFIDS LEKTDEDKYK
     VTLKYPHYFP VMKKCCVPET RRKMEMAFHT RCKEENTIIL QQLLPLRAQV AKLLGYNTHA
     DFVLELNTAK STSHVATFLD DLSQKLKPLG EAEREFILSL KKKECEERGF AYDGKINAWD
     LHYYMTQTEE LKYSVDQESL KEYFPIEVVT EGLLSIYQEL LGLSFEQVAD AHVWNKSVSL
     YTVKDKATGE VLGQFYLDLY PREGKYNHAA CFGLQPGCLL PDGSRMMSVA ALVVNFSQPI
     AGRPSLLRHD EVRTYFHEFG HVMHQICAQT DFARFSGTNV ETDFVEVPSQ MLENWVWDID
     SLRKLSKHYR DGHPITDELL EKLVASRLVN TGLLTLRQIV LSKVDQSLHT NASLDAASEY
     AKYCTEILGV AATPGTNMPA TFGHLAGGYD GQYYGYLWSE VFSMDMFHSC FRKEGIMNPE
     VGMKYRNLIL KPGGSLDGMD MLQNFLQREP NQKAFLMSRG LNAS
//