NEUL_MOUSE
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 03-AUG-2022, entry version 144.
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, Pancreas,
RC 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; Q91YP2; -.
DR PeptideAtlas; Q91YP2; -.
DR PRIDE; Q91YP2; -.
DR ProteomicsDB; 252952; -.
DR Antibodypedia; 23804; 282 antibodies from 26 providers.
DR DNASU; 75805; -.
DR Ensembl; ENSMUST00000109315; ENSMUSP00000104938; ENSMUSG00000021710.
DR GeneID; 75805; -.
DR KEGG; mmu:75805; -.
DR UCSC; uc007rsp.1; mouse.
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; KRSGAWC; -.
DR OrthoDB; 642479at2759; -.
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 73 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 245 other tissues.
DR ExpressionAtlas; Q91YP2; baseline and differential.
DR Genevisible; Q91YP2; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
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: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 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; 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
