THOP1_RAT
ID THOP1_RAT Reviewed; 687 AA.
AC P24155; Q66HS4;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 4.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Thimet oligopeptidase;
DE EC=3.4.24.15 {ECO:0000269|PubMed:12500972};
DE AltName: Full=Endo-oligopeptidase A;
DE AltName: Full=Endopeptidase 24.15;
DE AltName: Full=PZ-peptidase;
DE AltName: Full=Soluble metallo-endopeptidase;
GN Name=Thop1;
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], PARTIAL PROTEIN SEQUENCE, AND FUNCTION.
RC TISSUE=Testis;
RX PubMed=2261476; DOI=10.1021/bi00497a006;
RA Pierotti A., Dong K.-W., Glucksman M.J., Orlowski M., Roberts J.L.;
RT "Molecular cloning and primary structure of rat testes metalloendopeptidase
RT EC 3.4.24.15.";
RL Biochemistry 29:10323-10329(1990).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=8216239; DOI=10.1042/bj2950057;
RA McKie N., Dando P.M., Rawlings N.D., Barrett A.J.;
RT "Thimet oligopeptidase: similarity to 'soluble angiotensin II-binding
RT protein' and some corrections to the published amino acid sequence of the
RT rat testis enzyme.";
RL Biochem. J. 295:57-60(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 PROTEIN SEQUENCE OF 35-45; 267-273; 311-317; 351-357; 411-418 AND 560-578,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
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: Involved in the metabolism of neuropeptides under 20 amino
CC acid residues long (PubMed:2261476). 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
CC (PubMed:12500972, PubMed:18077343). {ECO:0000250|UniProtKB:P52888,
CC ECO:0000269|PubMed:12500972, ECO:0000269|PubMed:18077343,
CC ECO:0000269|PubMed:2261476}.
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:0000269|PubMed:12500972};
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 -!- INTERACTION:
CC P24155; P62161: Calm3; NbExp=2; IntAct=EBI-6372841, EBI-397530;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P47788}.
CC -!- TISSUE SPECIFICITY: Expressed abundantly in the testis. It is also
CC found in the liver, lung and kidney. {ECO:0000269|PubMed:2261476}.
CC -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR EMBL; M61142; AAA41586.1; -; mRNA.
DR EMBL; BC081706; AAH81706.1; -; mRNA.
DR PIR; S38760; HYRTTH.
DR RefSeq; NP_742072.2; NM_172075.2.
DR AlphaFoldDB; P24155; -.
DR SMR; P24155; -.
DR BioGRID; 249102; 1.
DR ELM; P24155; -.
DR IntAct; P24155; 5.
DR STRING; 10116.ENSRNOP00000027045; -.
DR MEROPS; M03.001; -.
DR iPTMnet; P24155; -.
DR PhosphoSitePlus; P24155; -.
DR jPOST; P24155; -.
DR PaxDb; P24155; -.
DR PRIDE; P24155; -.
DR Ensembl; ENSRNOT00000027045; ENSRNOP00000027045; ENSRNOG00000019924.
DR GeneID; 64517; -.
DR KEGG; rno:64517; -.
DR UCSC; RGD:68330; rat.
DR CTD; 7064; -.
DR RGD; 68330; Thop1.
DR eggNOG; KOG2089; Eukaryota.
DR GeneTree; ENSGT00950000183171; -.
DR HOGENOM; CLU_001805_2_1_1; -.
DR InParanoid; P24155; -.
DR OMA; KNFQSAM; -.
DR OrthoDB; 642479at2759; -.
DR PhylomeDB; P24155; -.
DR TreeFam; TF300459; -.
DR BRENDA; 3.4.24.15; 5301.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:P24155; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000019924; Expressed in testis and 20 other tissues.
DR ExpressionAtlas; P24155; baseline and differential.
DR Genevisible; P24155; RN.
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; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA:UniProtKB.
DR GO; GO:0006518; P:peptide metabolic process; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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; Direct protein sequencing; Hydrolase;
KW Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..687
FT /note="Thimet oligopeptidase"
FT /id="PRO_0000078155"
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:0000250|UniProtKB:Q8C1A5"
FT MOD_RES 257
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P52888"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8C1A5"
FT MOD_RES 538
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P52888"
FT CONFLICT 321
FT /note="C -> S (in Ref. 1; AAA41586)"
FT /evidence="ECO:0000305"
FT CONFLICT 347..348
FT /note="TR -> DS (in Ref. 1; AAA41586)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 687 AA; 78385 MW; A0B399AF61B60F81 CRC64;
MKPPAACAGD VVDTVSPCST VNHLRWDLSA QQIRALTTQL IEQTKCVYDR VGAQDFEDVS
YESTLKALAD VEVTYTVQRN ILDFPQHVSP NKDIRAASTE ADKKLSEFDV EMSMRQDVYQ
RVVWLQEKIP KDSLKPEAAR YLERLIKLGR RNGLHLPQDT QEKIKNIKKR LSLLCIDFNK
NLNEDTTFLP FTREELGGLP EDFLNSLEKT EDGKLKVTLK YPHYFPLLKK CHVPETRRLL
EEAFNCRCKE ENCAILKELV SLRAQKSNLL GFRTHADYVL EMNMAKTSQT VATFLDELAR
KLKPLGEQER AVILELKEAE CAKRGLPFDG RIHAWDMRYY MNQVEETRYR VDQNLLKEYF
PMQVVTRGLL AIYQELLGLT FTLEEGAAAW HEDVRLYSVR DAASGEEIGK FYLDLYPREG
KYGHAACFGL QPGCLRQDGS RQLAIAAMVA NFTKPTPDVP SLLQHDEVET YFHEFGHVMH
QLCSQAEFAM FSGTHVERDF VEAPSQMLEN WVWEKEPLMR MSQHYRTGGE APEDLLEKLI
KSRQANAGLF NLRQIVLAKV DQVLHTQTDV DPAEEYARLC QEILGVPATP GTNMPATFGH
LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLSPKVGMD YRTSILRPGG SEDASTMLKQ
FLGRDPKQDA FLLSKGLQVE GCEPPAC
