LOCUS       NM_003249               4761 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens thimet oligopeptidase 1 (THOP1), mRNA.
ACCESSION   NM_003249
VERSION     NM_003249.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4761)
  AUTHORS   Neves,R.L., Marem,A., Carmona,B., Arata,J.G., Cyrillo Ramos,M.P.,
            Justo,G.Z., Machado de Melo,F.H., Oliveira,V. and Icimoto,M.Y.
  TITLE     Expression of thimet oligopeptidase (THOP) modulated by oxidative
            stress in human multidrug resistant (MDR) leukemia cells
  JOURNAL   Biochimie 212, 21-30 (2023)
   PUBMED   36997147
  REMARK    GeneRIF: Expression of thimet oligopeptidase (THOP) modulated by
            oxidative stress in human multidrug resistant (MDR) leukemia cells.
REFERENCE   2  (bases 1 to 4761)
  AUTHORS   Ferro,E.S., Gewehr,M.C.F. and Navon,A.
  TITLE     Thimet Oligopeptidase Biochemical and Biological Significances:
            Past, Present, and Future Directions
  JOURNAL   Biomolecules 10 (9), 1229 (2020)
   PUBMED   32847123
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4761)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   4  (bases 1 to 4761)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 4761)
  AUTHORS   Shchetynsky,K., Diaz-Gallo,L.M., Folkersen,L., Hensvold,A.H.,
            Catrina,A.I., Berg,L., Klareskog,L. and Padyukov,L.
  TITLE     Discovery of new candidate genes for rheumatoid arthritis through
            integration of genetic association data with expression pathway
            analysis
  JOURNAL   Arthritis Res Ther 19 (1), 19 (2017)
   PUBMED   28148290
  REMARK    GeneRIF: Data suggest that three new candidate genes involved in
            the development of rheumatoid arthritis (RA): ERBB2, TP53 and
            THOP1.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4761)
  AUTHORS   Torres,M.P., Prange,C. and Lennon,G.
  TITLE     Human endopeptidase 24.15 (THOP1) is localized on chromosome
            19p13.3 and is excluded from the linkage region for late-onset
            Alzheimer disease
  JOURNAL   Genomics 53 (2), 239-240 (1998)
   PUBMED   9790774
REFERENCE   7  (bases 1 to 4761)
  AUTHORS   Meckelein,B., de Silva,H.A., Roses,A.D., Rao,P.N., Pettenati,M.J.,
            Xu,P.T., Hodge,R., Glucksman,M.J. and Abraham,C.R.
  TITLE     Human endopeptidase (THOP1) is localized on chromosome 19 within
            the linkage region for the late-onset alzheimer disease AD2 locus
  JOURNAL   Genomics 31 (2), 246-249 (1996)
   PUBMED   8824811
REFERENCE   8  (bases 1 to 4761)
  AUTHORS   Thompson,A., Huber,G. and Malherbe,P.
  TITLE     Cloning and functional expression of a metalloendopeptidase from
            human brain with the ability to cleave a beta-APP substrate peptide
  JOURNAL   Biochem Biophys Res Commun 213 (1), 66-73 (1995)
   PUBMED   7639763
REFERENCE   9  (bases 1 to 4761)
  AUTHORS   Papastoitsis,G., Siman,R., Scott,R. and Abraham,C.R.
  TITLE     Identification of a metalloprotease from Alzheimer's disease brain
            able to degrade the beta-amyloid precursor protein and generate
            amyloidogenic fragments
  JOURNAL   Biochemistry 33 (1), 192-199 (1994)
   PUBMED   8286339
REFERENCE   10 (bases 1 to 4761)
  AUTHORS   Dando,P.M., Brown,M.A. and Barrett,A.J.
  TITLE     Human thimet oligopeptidase
  JOURNAL   Biochem J 294 (Pt 2) (Pt 2), 451-457 (1993)
   PUBMED   8373360
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BU849088.1, BC002391.2,
            BU741442.1 and AC006538.1.
            
            On Nov 22, 2018 this sequence version replaced NM_003249.4.
            
            Summary: The protein encoded by this gene is a kininase that uses
            zinc as a cofactor. The encoded oligopeptidase cleaves cytosolic
            peptides, making them unavailable for display on antigen-presenting
            cells. This protein also cleaves neuropeptides under 20 aa in
            length and can degrade beta-amyloid precursor protein to
            amyloidogenic peptides. [provided by RefSeq, Nov 2015].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660805.110060.1, BC002391.2
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000307741.11/ ENSP00000304467.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-5                 BU849088.1         44-48
            6-2555              BC002391.2         1-2550
            2556-2558           BU741442.1         17-19               c
            2559-4761           AC006538.1         168805-171007
FEATURES             Location/Qualifiers
     source          1..4761
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.3"
     gene            1..4761
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /note="thimet oligopeptidase 1"
                     /db_xref="GeneID:7064"
                     /db_xref="HGNC:HGNC:11793"
                     /db_xref="MIM:601117"
     exon            1..176
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     CDS             161..2230
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /EC_number="3.4.24.15"
                     /note="endopeptidase 24.15"
                     /codon_start=1
                     /product="thimet oligopeptidase"
                     /protein_id="NP_003240.1"
                     /db_xref="CCDS:CCDS12095.1"
                     /db_xref="GeneID:7064"
                     /db_xref="HGNC:HGNC:11793"
                     /db_xref="MIM:601117"
                     /translation="MKPPAACAGDMADAASPCSVVNDLRWDLSAQQIEERTRELIEQT
                     KRVYDQVGTQEFEDVSYESTLKALADVEVTYTVQRNILDFPQHVSPSKDIRTASTEAD
                     KKLSEFDVEMSMREDVYQRIVWLQEKVQKDSLRPEAARYLERLIKLGRRNGLHLPRET
                     QENIKRIKKKLSLLCIDFNKNLNEDTTFLPFTLQELGGLPEDFLNSLEKMEDGKLKVT
                     LKYPHYFPLLKKCHVPETRRKVEEAFNCRCKEENCAILKELVTLRAQKSRLLGFHTHA
                     DYVLEMNMAKTSQTVATFLDELAQKLKPLGEQERAVILELKRAECERRGLPFDGRIRA
                     WDMRYYMNQVEETRYCVDQNLLKEYFPVQVVTHGLLGIYQELLGLAFHHEEGASAWHE
                     DVRLYTARDAASGEVVGKFYLDLYPREGKYGHAACFGLQPGCLRQDGSRQIAIAAMVA
                     NFTKPTADAPSLLQHDEVETYFHEFGHVMHQLCSQAEFAMFSGTHVERDFVEAPSQML
                     ENWVWEQEPLLRMSRHYRTGSAVPRELLEKLIESRQANTGLFNLRQIVLAKVDQALHT
                     QTDADPAEEYARLCQEILGVPATPGTNMPATFGHLAGGYDAQYYGYLWSEVYSMDMFH
                     TRFKQEGVLNSKVGMDYRSCILRPGGSEDASAMLRRFLGRDPKQDAFLLSKGLQVGGC
                     EPEPQVC"
     exon            177..389
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            390..538
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            539..646
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            647..749
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            750..910
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            911..1046
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            1047..1413
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            1414..1615
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            1616..1802
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            1803..1931
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            1932..2068
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     exon            2069..4761
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2532..2537
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /note="hexamer: ATTAAA"
     polyA_site      2553
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /note="major polyA site"
     regulatory      4739..4744
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
                     /note="hexamer: AATAAA"
     polyA_site      4761
                     /gene="THOP1"
                     /gene_synonym="EP24.15; MEPD_HUMAN; MP78; TOP"
ORIGIN      
        1 agcatgcccc gggagcgcgg gcggcgggcc ccttggtcct caggcggccg tggcggcggt
       61 ggcggcggtt gggccgaggc aggcggcctc agtggccgag gtggctggac gcgtagcagg
      121 tggaaggagg gagggagccg caggcgcaga cccacccgcc atgaagcccc ccgcagcctg
      181 tgcaggagac atggcggacg cagcatctcc gtgctctgtg gtaaacgacc tgcggtggga
      241 cctgagtgcc cagcagatag aggagcgcac cagggagctc atcgagcaga ccaagcgcgt
      301 gtatgaccag gttggcaccc aggagtttga ggacgtgtcc tacgagagca cgctcaaggc
      361 gctggccgat gtggaggtca cctacacagt tcagaggaat atccttgact tcccccagca
      421 tgtttccccc tccaaggaca tccggacagc cagcacagag gccgacaaga agctctctga
      481 gttcgacgtg gagatgagca tgagggagga cgtgtaccag aggatcgtgt ggctccagga
      541 gaaagttcag aaggactcac tgaggcccga ggctgcgcgg tacctggagc ggctaatcaa
      601 gctgggccgg agaaatgggc ttcacctccc cagagagact caggaaaaca tcaaacgcat
      661 caagaagaag ctgagccttc tgtgcatcga cttcaacaag aacctgaacg aggacacgac
      721 cttcctgccc ttcacgctcc aggagctagg agggctcccc gaggactttc tgaactccct
      781 ggagaagatg gaggacggca agttgaaggt caccctcaag tacccccatt acttccccct
      841 cctgaagaaa tgccacgtgc ctgagaccag gaggaaagtg gaggaggcct tcaactgccg
      901 gtgcaaggag gagaactgcg ctatcctcaa ggagctggtg acgctgcggg cccagaagtc
      961 ccgcctgctg gggttccaca cgcacgccga ctatgtcctg gagatgaaca tggccaagac
     1021 cagccagacc gtggccacct tcctagatga gctggcgcag aagctgaagc ccctggggga
     1081 gcaggagcgt gcggtgattc tggagctgaa gcgtgcggag tgcgagcgcc ggggcctgcc
     1141 cttcgacggc cgcatccgtg cctgggacat gcgctactac atgaaccagg tggaggagac
     1201 gcgctactgc gtggaccaga acctgctcaa ggagtacttc cccgtgcagg tggtcacgca
     1261 cgggctgctg ggcatctacc aggagctcct ggggctggcc ttccaccacg aggagggcgc
     1321 cagtgcctgg catgaggacg tgcggctcta caccgcgagg gacgcggcct cgggggaggt
     1381 ggtcggcaag ttctacctgg acctgtaccc gcgggaagga aagtacgggc acgcggcctg
     1441 ctttggcctg cagcccggct gcctgcggca ggatgggagc cgccagatcg ccatcgcggc
     1501 catggtggcc aacttcacca agcccacagc cgacgcgccc tcgctgctgc agcatgacga
     1561 ggtggagacc tacttccatg agtttggcca cgtgatgcac cagctctgct cccaggcgga
     1621 gttcgccatg ttcagcggga cccacgtgga gcgggacttt gtggaggcgc cgtcgcagat
     1681 gctggagaac tgggtgtggg agcaggagcc gctgctgcgg atgtcgcggc actaccgcac
     1741 aggcagcgcc gtgccccggg agctcctgga gaagctcatt gagtcccggc aggccaacac
     1801 aggcctcttc aacctgcgcc agatcgtcct cgccaaggtg gaccaggccc tgcacacgca
     1861 gacggacgca gaccccgccg aggagtatgc gcggctctgc caggagatcc tcggggtccc
     1921 ggccacgcca ggaaccaaca tgcctgcaac cttcggccat ctggcaggtg gctacgacgc
     1981 ccagtactac gggtacctgt ggagcgaggt gtattccatg gacatgttcc acacgcgctt
     2041 caagcaggag ggtgtcctga acagcaaggt tggcatggat tacagaagct gcatcctgag
     2101 acccggcggt tccgaggatg ccagcgccat gctgaggcgc ttcctgggcc gtgaccccaa
     2161 gcaggacgcc ttcctcctga gcaaggggct gcaggtcggg ggctgcgagc ccgagccgca
     2221 ggtctgctga ggcctggcac tgcgactgcc cagtctggcc tgcgctcccg ccgccctggt
     2281 gccttagccc ccggcacagg atggggcagg ctctggcaca gtgcctggga ctggcagggt
     2341 ggctgagcgg ctgtcttgcc tcttgtcatt gtctgtcccc acccggtcgt ggcccacccg
     2401 gctagagacg gcgtcctcaa ggcatctgga gggctttcgt ggctgccagg gcctggtctt
     2461 tgttgcacta acacgtctcc tctctgggaa acgtcccttg tcaggagacg gctcttcttt
     2521 gaaatgaggt cattaaaagg aaacagaaaa agagagaggc tccctggcct ggtcactggc
     2581 tcctgcgctt ttttggtccg aggacggtgg gacggcgggt cagggtccag ccctcgggct
     2641 gttgccacac caggccctgg attggggctc aggtccttgt gggggcgggg ggtgggggag
     2701 taaagggctg ggaaccagtt ctgccagcca ggccggcctg gggggtctga gagacttcgg
     2761 cttcctgcat gcttctcacc tgttgtcatt ctggaacatt ccccccgccc tgctcagctc
     2821 tggccatcaa ggaccaggct ccactggtca gagagtctgg aaagtcaggg caggccctgt
     2881 gcgcacaggc agccggggcg gggctggggg tcagcagctg cccaccctct catccacagg
     2941 ggaaggccgg gctcactcca gcttcctagg cagagtctct gggggttcct gttggacaca
     3001 agtgaaccag gtgaaccagg gcagctgctg gaagctcggc catggccctc atcctcatgg
     3061 ccttggggac tgcctgtgcc tgccctccct ggcggcccca ctcccctggc tgtgggcaac
     3121 atggcaaagt cttgatcggg ggtgcagggt cgggggggcg cttcctggac cctccaacag
     3181 tgctcagaga tgcctcaggg atagctgtcg gctgtgtccc cacctcccga gcaagacaag
     3241 tggatgctcc ccgtctcttc agtcccagtg ctctgatgtt ttctcccgcg actgtgagtt
     3301 tctcaggagc ccccctcgtg ccctgggagc gtccctcccc agtcttagtc ctccacgaag
     3361 gacgctggtc agcagaacct gtgaccctgc ttcccgaggc ctatgggtgg ccagacatcc
     3421 gcctcgtcct cacctccatt tggacaggac tccgagggct gtgccatctg cttcagcccc
     3481 tcctgtccca ttcccaccca gcccaggtca gtgtggctgt ggccactgcc atggggcctg
     3541 ctttgcacct tacgcacgcc tggctctgct ccatgcacct gcttctgtgt ctttccaact
     3601 ctgggggcta aggggtgagt cttgtctttg cagagctgga cggcacagcc tgtggccagg
     3661 agggttatgc cagcgaggcg ggaatccata agtgggaaca ccacagtggt cacgtttcag
     3721 atactcacag ctcagagcgg gtcccatagc ttgcacctga agccccaact actcaggagg
     3781 ctgaggcgga aggattgctt gagcccagga gggcaaggcc agcctgggca acgtggcaag
     3841 accccatctc taaaaaaaat aagttcggtg ggtgtggggc cagtgcctgt ggtctgtttt
     3901 ttgggaggct gaggcaggag gatcgcttga gcctaggagg tcaaggctgc agtaagccgt
     3961 gatcccacca ctgcactgca gcctgggcaa cagagcaaga ctgtctctaa aataacaata
     4021 ataataaaat acctggggtt cagaaaagaa aagctggaag gcaaagccga ccgcactggg
     4081 cagaggtgga gatggcaagt ctgggggctc cctcatcttc ccctgccccg agccctcagg
     4141 tggcctccac ctggtcccca gcgaagtccc agttgtgcaa gagcacccca gctgggccct
     4201 gggccatcac agccttgtca cacacacagc ctggcccatc acagcagagc tggggtcaca
     4261 gccttgggct gctgggccgt gggcggatgg cctggaccat ccacacccca ctcccctgga
     4321 agtcaccaac tgggcttagt tgccggatac cccaggcagc cccccgcggt gcttcgcaag
     4381 ttgggccgcc tcccccagca tgtcccctgc tctgtggaca cccagggatg tggaggtagt
     4441 agcacagagt ctcggtccag ggccctgttc cccagggagc tgggcgtcct cagagccttc
     4501 ccaaatgccc acaccggggg cacccgggtt tccccaaaca ctccaggaca gagcgggggc
     4561 tttgatcaca gggagggggc tgcagagctg ctgtgtctcc tggctcctct gccccatgct
     4621 ccccactcag ggctccagca gtgggctcag aggacagtgt ggcattagca tcccctgccc
     4681 gtccaggttg tcactctcct tggccccttg ctgctcccca gtggaaaaaa aagggggaaa
     4741 taaagaatcg taaaaaatac a
//
