ID   THOP1_MOUSE             Reviewed;         687 AA.
AC   Q8C1A5; Q8K0J9; Q8K2D4; Q9EPX1;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   08-NOV-2023, entry version 133.
DE   RecName: Full=Thimet oligopeptidase;
DE            EC=3.4.24.15 {ECO:0000305|PubMed:10969067};
GN   Name=Thop1;
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 [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=10969067; DOI=10.1074/jbc.m001843200;
RA   Tullai J.W., Cummins P.M., Pabon A., Roberts J.L., Lopingco M.C.,
RA   Shrimpton C.N., Smith A.I., Martignetti J.A., Ferro E.S., Glucksman M.J.;
RT   "The neuropeptide processing enzyme EC 3.4.24.15 is modulated by protein
RT   kinase A phosphorylation.";
RL   J. Biol. Chem. 275:36514-36522(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Skin;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II, and FVB/N; TISSUE=Colon, and 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   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-278, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=18034455; DOI=10.1021/pr0701254;
RA   Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT   "Large-scale identification and evolution indexing of tyrosine
RT   phosphorylation sites from murine brain.";
RL   J. Proteome Res. 7:311-318(2008).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-172, AND IDENTIFICATION BY
RP   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: Involved in the metabolism of neuropeptides under 20 amino
CC       acid residues long (PubMed:10969067). Involved in cytoplasmic peptide
CC       degradation. Able to degrade the amyloid-beta precursor protein and
CC       generate amyloidogenic fragments (By similarity). Also acts as a
CC       regulator of cannabinoid signaling pathway by mediating degradation of
CC       hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By
CC       similarity). {ECO:0000250|UniProtKB:P24155,
CC       ECO:0000250|UniProtKB:P52888, ECO:0000269|PubMed:10969067}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage of bonds with hydrophobic residues at
CC         P1, P2 and P3' and a small residue at P1' in substrates of 5 to 15
CC         residues.; EC=3.4.24.15; Evidence={ECO:0000305|PubMed:10969067};
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   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P47788}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P47788}.
CC   -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR   EMBL; AF314187; AAG35061.1; -; mRNA.
DR   EMBL; AK028609; BAC26031.1; -; mRNA.
DR   EMBL; BC031175; AAH31175.1; -; mRNA.
DR   EMBL; BC031722; AAH31722.1; -; mRNA.
DR   CCDS; CCDS24042.1; -.
DR   RefSeq; NP_073144.3; NM_022653.4.
DR   AlphaFoldDB; Q8C1A5; -.
DR   SMR; Q8C1A5; -.
DR   BioGRID; 206040; 20.
DR   STRING; 10090.ENSMUSP00000005057; -.
DR   MEROPS; M03.001; -.
DR   GlyGen; Q8C1A5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8C1A5; -.
DR   PhosphoSitePlus; Q8C1A5; -.
DR   SwissPalm; Q8C1A5; -.
DR   REPRODUCTION-2DPAGE; Q8C1A5; -.
DR   EPD; Q8C1A5; -.
DR   MaxQB; Q8C1A5; -.
DR   PaxDb; 10090-ENSMUSP00000005057; -.
DR   PeptideAtlas; Q8C1A5; -.
DR   ProteomicsDB; 259022; -.
DR   Pumba; Q8C1A5; -.
DR   DNASU; 50492; -.
DR   GeneID; 50492; -.
DR   KEGG; mmu:50492; -.
DR   UCSC; uc007gfv.2; mouse.
DR   AGR; MGI:1354165; -.
DR   CTD; 7064; -.
DR   MGI; MGI:1354165; Thop1.
DR   eggNOG; KOG2089; Eukaryota.
DR   InParanoid; Q8C1A5; -.
DR   OrthoDB; 735202at2759; -.
DR   PhylomeDB; Q8C1A5; -.
DR   TreeFam; TF300459; -.
DR   BRENDA; 3.4.24.15; 3474.
DR   Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   BioGRID-ORCS; 50492; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Thop1; mouse.
DR   PRO; PR:Q8C1A5; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8C1A5; Protein.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:MGI.
DR   GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR   GO; GO:0042277; F:peptide binding; ISO:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR   GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR   GO; GO:0006518; P:peptide metabolic process; IDA:MGI.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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; PROTEASE M3 THIMET OLIGOPEPTIDASE-RELATED; 1.
DR   PANTHER; PTHR11804:SF50; THIMET OLIGOPEPTIDASE; 1.
DR   Pfam; PF01432; Peptidase_M3; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Hydrolase; Metal-binding; Metalloprotease;
KW   Phosphoprotein; Protease; Reference proteome; Zinc.
FT   CHAIN           1..687
FT                   /note="Thimet oligopeptidase"
FT                   /id="PRO_0000319044"
FT   ACT_SITE        474
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         473
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         477
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         480
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   MOD_RES         16
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52888"
FT   MOD_RES         172
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         257
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P52888"
FT   MOD_RES         278
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:18034455"
FT   MOD_RES         538
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P52888"
FT   CONFLICT        132
FT                   /note="N -> D (in Ref. 1; AAG35061 and 3; AAH31722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        193..194
FT                   /note="RE -> KK (in Ref. 1; AAG35061)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        205
FT                   /note="S -> I (in Ref. 1; AAG35061)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        529
FT                   /note="S -> G (in Ref. 1; AAG35061)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   687 AA;  78026 MW;  362D899CE5101662 CRC64;
     MKPPAACAGD VVDAASPAST VNHLRWDLSA QQIRALTTQL IEQTKCVYDR VGAQNFEDVS
     YESTLKALAD VEVTYTVQRN ILDFPQHVSP CKDIRAASTE ADKKLSEFDV EMSMRQDVYQ
     RVVWLQEKTP KNSLKPEAAR YLERLIKLGR RNGLHLPQDT QEKIKNIKKR LSLLCIDFNK
     NLNEDTTFLP FTREELGGLP EDFLSSLEKA EDGKLKVTLK YPHYFPLLKK CHVPETRRLL
     EEAFNCRCKE ENCAILKELV SLRAQKSSLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ
     KLKPLGEQER AVILELKEAE CAKRGLPFDG RIHAWDMRYY MNQVEETRYR VDQNLLKEYF
     PMQVVTRGLL AIYQELLGLT FTLEEGAAAW HEDVRLYSVR DAASGEEIGK FYLDLYPREG
     KYGHAACFGL QPGCLRQDGS RQLAVAAMVA NFTKPTPDAP SLLQHDEVET YFHEFGHVMH
     QLCSQAEFAM FSGTHVERDF VEAPSQMLEN WVWEKEPLMR MSQHYRTGSE APQDLLEKLI
     KSRQANAGLF NLRQIVLAKV DQVLHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH
     LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLSPKVGMD YRTSILRPGG SEDASAMLKQ
     FLGRDPKQDA FLLSKGLQVE GSEAPAC
//