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, 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: 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
//
