Full text data of THOP1
THOP1
[Confidence: low (only semi-automatic identification from reviews)]
Thimet oligopeptidase; 3.4.24.15 (Endopeptidase 24.15; MP78)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Thimet oligopeptidase; 3.4.24.15 (Endopeptidase 24.15; MP78)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P52888
ID THOP1_HUMAN Reviewed; 689 AA.
AC P52888; Q9UCB3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Thimet oligopeptidase;
DE EC=3.4.24.15;
DE AltName: Full=Endopeptidase 24.15;
DE AltName: Full=MP78;
GN Name=THOP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7639763; DOI=10.1006/bbrc.1995.2099;
RA Thompson A., Huber G., Malherbe P.;
RT "Cloning and functional expression of a metalloendopeptidase from
RT human brain with the ability to cleave a beta-APP substrate peptide.";
RL Biochem. Biophys. Res. Commun. 213:66-73(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Taylor G.R., Otulakowski G., Lau C.Y., Munroe D.G.;
RT "cDNA cloning and gene structure of a human gene encoding a highly
RT conserved metalloendopeptidase (EC 3.4.24.15).";
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 67-78; 181-197 AND 199-200.
RC TISSUE=Brain;
RX PubMed=8286339; DOI=10.1021/bi00167a025;
RA Papastoitsis G., Siman R., Scott R., Abraham C.R.;
RT "Identification of a metalloprotease from Alzheimer's disease brain
RT able to degrade the beta-amyloid precursor protein and generate
RT amyloidogenic fragments.";
RL Biochemistry 33:192-199(1994).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-257 AND LYS-538, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 16-688, AND ZINC-BINDING
RP SITES.
RX PubMed=17251185; DOI=10.1074/jbc.M609897200;
RA Lim E.J., Sampath S., Coll-Rodriguez J., Schmidt J., Ray K.,
RA Rodgers D.W.;
RT "Swapping the substrate specificities of the neuropeptidases
RT neurolysin and thimet oligopeptidase.";
RL J. Biol. Chem. 282:9722-9732(2007).
CC -!- FUNCTION: Involved in the metabolism of neuropeptides under 20
CC amino acid residues long. Involved in cytoplasmic peptide
CC degradation. Able to degrade the beta-amyloid precursor protein
CC and generate amyloidogenic fragments.
CC -!- CATALYTIC ACTIVITY: Preferential cleavage of bonds with
CC hydrophobic residues at P1, P2 and P3' and a small residue at P1'
CC in substrates of 5 to 15 residues.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- INTERACTION:
CC P62161:Calm3 (xeno); NbExp=2; IntAct=EBI-372399, EBI-397530;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the peptidase M3 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; Z50115; CAA90477.1; -; mRNA.
DR EMBL; U29366; AAA82607.1; -; mRNA.
DR EMBL; AC006538; AAD13118.1; -; Genomic_DNA.
DR EMBL; BC000135; AAH00135.1; -; mRNA.
DR EMBL; BC002391; AAH02391.1; -; mRNA.
DR PIR; JC4197; HYHUTH.
DR RefSeq; NP_003240.1; NM_003249.3.
DR UniGene; Hs.78769; -.
DR PDB; 1S4B; X-ray; 2.00 A; P=16-688.
DR PDB; 2O36; X-ray; 1.95 A; A=16-688.
DR PDBsum; 1S4B; -.
DR PDBsum; 2O36; -.
DR ProteinModelPortal; P52888; -.
DR SMR; P52888; 24-677.
DR IntAct; P52888; 3.
DR MINT; MINT-3019782; -.
DR STRING; 9606.ENSP00000304467; -.
DR MEROPS; M03.001; -.
DR PhosphoSite; P52888; -.
DR DMDM; 1708983; -.
DR PaxDb; P52888; -.
DR PeptideAtlas; P52888; -.
DR PRIDE; P52888; -.
DR DNASU; 7064; -.
DR Ensembl; ENST00000307741; ENSP00000304467; ENSG00000172009.
DR GeneID; 7064; -.
DR KEGG; hsa:7064; -.
DR UCSC; uc002lwj.3; human.
DR CTD; 7064; -.
DR GeneCards; GC19P002785; -.
DR HGNC; HGNC:11793; THOP1.
DR HPA; CAB025497; -.
DR MIM; 601117; gene.
DR neXtProt; NX_P52888; -.
DR PharmGKB; PA36505; -.
DR eggNOG; COG0339; -.
DR HOGENOM; HOG000245985; -.
DR HOVERGEN; HBG000238; -.
DR InParanoid; P52888; -.
DR KO; K01392; -.
DR OMA; KVIDAQN; -.
DR OrthoDB; EOG7SR4KW; -.
DR PhylomeDB; P52888; -.
DR EvolutionaryTrace; P52888; -.
DR GeneWiki; THOP1; -.
DR GenomeRNAi; 7064; -.
DR NextBio; 27623; -.
DR PMAP-CutDB; P52888; -.
DR PRO; PR:P52888; -.
DR ArrayExpress; P52888; -.
DR Bgee; P52888; -.
DR CleanEx; HS_THOP1; -.
DR Genevestigator; P52888; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; TAS:ProtInc.
DR GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0006518; P:peptide metabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1370.10; -; 2.
DR Gene3D; 1.20.1050.40; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom.
DR InterPro; IPR024077; Neurolysin/TOP_dom2.
DR InterPro; IPR024080; Neurolysin/TOP_N.
DR InterPro; IPR001567; Pept_M3A_M3B.
DR Pfam; PF01432; Peptidase_M3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Zinc.
FT CHAIN 1 689 Thimet oligopeptidase.
FT /FTId=PRO_0000078153.
FT ACT_SITE 474 474
FT METAL 473 473 Zinc; catalytic.
FT METAL 477 477 Zinc; catalytic.
FT METAL 480 480 Zinc; catalytic.
FT MOD_RES 257 257 N6-acetyllysine.
FT MOD_RES 278 278 Phosphotyrosine (By similarity).
FT MOD_RES 538 538 N6-acetyllysine.
FT HELIX 30 52
FT HELIX 56 58
FT TURN 61 64
FT HELIX 65 83
FT HELIX 85 88
FT HELIX 92 113
FT HELIX 116 128
FT HELIX 136 151
FT TURN 152 155
FT HELIX 158 184
FT STRAND 188 191
FT TURN 193 198
FT HELIX 201 204
FT STRAND 207 209
FT STRAND 215 220
FT HELIX 221 230
FT HELIX 234 244
FT TURN 245 248
FT HELIX 249 269
FT HELIX 275 280
FT HELIX 288 324
FT TURN 334 336
FT HELIX 337 348
FT HELIX 353 356
FT HELIX 357 359
FT HELIX 362 377
FT STRAND 379 383
FT STRAND 395 401
FT TURN 402 404
FT STRAND 407 414
FT STRAND 426 431
FT STRAND 444 449
FT HELIX 465 483
FT HELIX 489 491
FT TURN 498 502
FT HELIX 503 509
FT HELIX 510 513
FT HELIX 515 520
FT TURN 525 527
FT HELIX 533 541
FT HELIX 542 544
FT HELIX 547 564
FT HELIX 572 582
FT HELIX 594 597
FT HELIX 599 602
FT TURN 606 610
FT HELIX 611 630
FT HELIX 635 644
FT TURN 645 648
FT HELIX 649 651
FT HELIX 654 662
FT HELIX 669 674
SQ SEQUENCE 689 AA; 78840 MW; 092D53DD63B322DE CRC64;
MKPPAACAGD MADAASPCSV VNDLRWDLSA QQIEERTREL IEQTKRVYDQ VGTQEFEDVS
YESTLKALAD VEVTYTVQRN ILDFPQHVSP SKDIRTASTE ADKKLSEFDV EMSMREDVYQ
RIVWLQEKVQ KDSLRPEAAR YLERLIKLGR RNGLHLPRET QENIKRIKKK LSLLCIDFNK
NLNEDTTFLP FTLQELGGLP EDFLNSLEKM EDGKLKVTLK YPHYFPLLKK CHVPETRRKV
EEAFNCRCKE ENCAILKELV TLRAQKSRLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ
KLKPLGEQER AVILELKRAE CERRGLPFDG RIRAWDMRYY MNQVEETRYC VDQNLLKEYF
PVQVVTHGLL GIYQELLGLA FHHEEGASAW HEDVRLYTAR DAASGEVVGK FYLDLYPREG
KYGHAACFGL QPGCLRQDGS RQIAIAAMVA NFTKPTADAP SLLQHDEVET YFHEFGHVMH
QLCSQAEFAM FSGTHVERDF VEAPSQMLEN WVWEQEPLLR MSRHYRTGSA VPRELLEKLI
ESRQANTGLF NLRQIVLAKV DQALHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH
LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLNSKVGMD YRSCILRPGG SEDASAMLRR
FLGRDPKQDA FLLSKGLQVG GCEPEPQVC
//
ID THOP1_HUMAN Reviewed; 689 AA.
AC P52888; Q9UCB3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Thimet oligopeptidase;
DE EC=3.4.24.15;
DE AltName: Full=Endopeptidase 24.15;
DE AltName: Full=MP78;
GN Name=THOP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7639763; DOI=10.1006/bbrc.1995.2099;
RA Thompson A., Huber G., Malherbe P.;
RT "Cloning and functional expression of a metalloendopeptidase from
RT human brain with the ability to cleave a beta-APP substrate peptide.";
RL Biochem. Biophys. Res. Commun. 213:66-73(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Taylor G.R., Otulakowski G., Lau C.Y., Munroe D.G.;
RT "cDNA cloning and gene structure of a human gene encoding a highly
RT conserved metalloendopeptidase (EC 3.4.24.15).";
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 67-78; 181-197 AND 199-200.
RC TISSUE=Brain;
RX PubMed=8286339; DOI=10.1021/bi00167a025;
RA Papastoitsis G., Siman R., Scott R., Abraham C.R.;
RT "Identification of a metalloprotease from Alzheimer's disease brain
RT able to degrade the beta-amyloid precursor protein and generate
RT amyloidogenic fragments.";
RL Biochemistry 33:192-199(1994).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-257 AND LYS-538, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 16-688, AND ZINC-BINDING
RP SITES.
RX PubMed=17251185; DOI=10.1074/jbc.M609897200;
RA Lim E.J., Sampath S., Coll-Rodriguez J., Schmidt J., Ray K.,
RA Rodgers D.W.;
RT "Swapping the substrate specificities of the neuropeptidases
RT neurolysin and thimet oligopeptidase.";
RL J. Biol. Chem. 282:9722-9732(2007).
CC -!- FUNCTION: Involved in the metabolism of neuropeptides under 20
CC amino acid residues long. Involved in cytoplasmic peptide
CC degradation. Able to degrade the beta-amyloid precursor protein
CC and generate amyloidogenic fragments.
CC -!- CATALYTIC ACTIVITY: Preferential cleavage of bonds with
CC hydrophobic residues at P1, P2 and P3' and a small residue at P1'
CC in substrates of 5 to 15 residues.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- INTERACTION:
CC P62161:Calm3 (xeno); NbExp=2; IntAct=EBI-372399, EBI-397530;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the peptidase M3 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; Z50115; CAA90477.1; -; mRNA.
DR EMBL; U29366; AAA82607.1; -; mRNA.
DR EMBL; AC006538; AAD13118.1; -; Genomic_DNA.
DR EMBL; BC000135; AAH00135.1; -; mRNA.
DR EMBL; BC002391; AAH02391.1; -; mRNA.
DR PIR; JC4197; HYHUTH.
DR RefSeq; NP_003240.1; NM_003249.3.
DR UniGene; Hs.78769; -.
DR PDB; 1S4B; X-ray; 2.00 A; P=16-688.
DR PDB; 2O36; X-ray; 1.95 A; A=16-688.
DR PDBsum; 1S4B; -.
DR PDBsum; 2O36; -.
DR ProteinModelPortal; P52888; -.
DR SMR; P52888; 24-677.
DR IntAct; P52888; 3.
DR MINT; MINT-3019782; -.
DR STRING; 9606.ENSP00000304467; -.
DR MEROPS; M03.001; -.
DR PhosphoSite; P52888; -.
DR DMDM; 1708983; -.
DR PaxDb; P52888; -.
DR PeptideAtlas; P52888; -.
DR PRIDE; P52888; -.
DR DNASU; 7064; -.
DR Ensembl; ENST00000307741; ENSP00000304467; ENSG00000172009.
DR GeneID; 7064; -.
DR KEGG; hsa:7064; -.
DR UCSC; uc002lwj.3; human.
DR CTD; 7064; -.
DR GeneCards; GC19P002785; -.
DR HGNC; HGNC:11793; THOP1.
DR HPA; CAB025497; -.
DR MIM; 601117; gene.
DR neXtProt; NX_P52888; -.
DR PharmGKB; PA36505; -.
DR eggNOG; COG0339; -.
DR HOGENOM; HOG000245985; -.
DR HOVERGEN; HBG000238; -.
DR InParanoid; P52888; -.
DR KO; K01392; -.
DR OMA; KVIDAQN; -.
DR OrthoDB; EOG7SR4KW; -.
DR PhylomeDB; P52888; -.
DR EvolutionaryTrace; P52888; -.
DR GeneWiki; THOP1; -.
DR GenomeRNAi; 7064; -.
DR NextBio; 27623; -.
DR PMAP-CutDB; P52888; -.
DR PRO; PR:P52888; -.
DR ArrayExpress; P52888; -.
DR Bgee; P52888; -.
DR CleanEx; HS_THOP1; -.
DR Genevestigator; P52888; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; TAS:ProtInc.
DR GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0006518; P:peptide metabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1370.10; -; 2.
DR Gene3D; 1.20.1050.40; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom.
DR InterPro; IPR024077; Neurolysin/TOP_dom2.
DR InterPro; IPR024080; Neurolysin/TOP_N.
DR InterPro; IPR001567; Pept_M3A_M3B.
DR Pfam; PF01432; Peptidase_M3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Zinc.
FT CHAIN 1 689 Thimet oligopeptidase.
FT /FTId=PRO_0000078153.
FT ACT_SITE 474 474
FT METAL 473 473 Zinc; catalytic.
FT METAL 477 477 Zinc; catalytic.
FT METAL 480 480 Zinc; catalytic.
FT MOD_RES 257 257 N6-acetyllysine.
FT MOD_RES 278 278 Phosphotyrosine (By similarity).
FT MOD_RES 538 538 N6-acetyllysine.
FT HELIX 30 52
FT HELIX 56 58
FT TURN 61 64
FT HELIX 65 83
FT HELIX 85 88
FT HELIX 92 113
FT HELIX 116 128
FT HELIX 136 151
FT TURN 152 155
FT HELIX 158 184
FT STRAND 188 191
FT TURN 193 198
FT HELIX 201 204
FT STRAND 207 209
FT STRAND 215 220
FT HELIX 221 230
FT HELIX 234 244
FT TURN 245 248
FT HELIX 249 269
FT HELIX 275 280
FT HELIX 288 324
FT TURN 334 336
FT HELIX 337 348
FT HELIX 353 356
FT HELIX 357 359
FT HELIX 362 377
FT STRAND 379 383
FT STRAND 395 401
FT TURN 402 404
FT STRAND 407 414
FT STRAND 426 431
FT STRAND 444 449
FT HELIX 465 483
FT HELIX 489 491
FT TURN 498 502
FT HELIX 503 509
FT HELIX 510 513
FT HELIX 515 520
FT TURN 525 527
FT HELIX 533 541
FT HELIX 542 544
FT HELIX 547 564
FT HELIX 572 582
FT HELIX 594 597
FT HELIX 599 602
FT TURN 606 610
FT HELIX 611 630
FT HELIX 635 644
FT TURN 645 648
FT HELIX 649 651
FT HELIX 654 662
FT HELIX 669 674
SQ SEQUENCE 689 AA; 78840 MW; 092D53DD63B322DE CRC64;
MKPPAACAGD MADAASPCSV VNDLRWDLSA QQIEERTREL IEQTKRVYDQ VGTQEFEDVS
YESTLKALAD VEVTYTVQRN ILDFPQHVSP SKDIRTASTE ADKKLSEFDV EMSMREDVYQ
RIVWLQEKVQ KDSLRPEAAR YLERLIKLGR RNGLHLPRET QENIKRIKKK LSLLCIDFNK
NLNEDTTFLP FTLQELGGLP EDFLNSLEKM EDGKLKVTLK YPHYFPLLKK CHVPETRRKV
EEAFNCRCKE ENCAILKELV TLRAQKSRLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ
KLKPLGEQER AVILELKRAE CERRGLPFDG RIRAWDMRYY MNQVEETRYC VDQNLLKEYF
PVQVVTHGLL GIYQELLGLA FHHEEGASAW HEDVRLYTAR DAASGEVVGK FYLDLYPREG
KYGHAACFGL QPGCLRQDGS RQIAIAAMVA NFTKPTADAP SLLQHDEVET YFHEFGHVMH
QLCSQAEFAM FSGTHVERDF VEAPSQMLEN WVWEQEPLLR MSRHYRTGSA VPRELLEKLI
ESRQANTGLF NLRQIVLAKV DQALHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH
LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLNSKVGMD YRSCILRPGG SEDASAMLRR
FLGRDPKQDA FLLSKGLQVG GCEPEPQVC
//
MIM
601117
*RECORD*
*FIELD* NO
601117
*FIELD* TI
*601117 THIMET OLIGOPEPTIDASE 1; THOP1
;;TOP
*FIELD* TX
CLONING
Proteases involved in the amyloidogenic processing of amyloid precursor
read moreprotein (APP; 104760) represent likely candidates for the site of
mutation in a form of familial Alzheimer disease (AD2; 104310).
Formation of toxic amyloid in the brain parenchyma and cerebral
vasculature in Alzheimer disease requires the proteolytic release of the
39- to 43-amino acid amyloid beta peptide from its precursor, APP.
Papastoitsis et al. (1994) purified and characterized a metalloprotease
from human Alzheimer disease brain that was able to cleave a synthetic
peptide encompassing the amino-terminus of amyloid beta peptide and
generate amyloidogenic fragments from recombinant human APP. Sequence
comparison revealed that this enzyme, THOP1, has high homology to the
previously described rat metalloendopeptidase 24.15 (EC 3.4.24.15). The
beta-secretase-like activity of the human enzyme in vitro in combination
with its localization in neurons and its co-localization with APP in
transport vesicles purified from rabbit optic nerve rendered this enzyme
an interesting candidate for amyloidogenic processing of APP.
By immunocytochemical and Western blot analysis of mouse pituitary
corticotrophic cells, Garrido et al. (1999) observed a punctate
distribution and variable intense nuclear staining for endogenous Thop1.
Thop1 colocalized with syntaxin-6 (STX6; 603944) in the juxtanuclear
region and was found in small vesicular organelles throughout the cell
body, colocalizing with ACTH in some organelles.
GENE FUNCTION
Most antigenic peptides presented on major histocompatibility complex
(MHC) class I molecules are generated by proteasomes during protein
processing. To determine if cytosolic peptidases destroy these peptides,
York et al. (2003) overexpressed TOP in cells. They found that TOP
overexpression reduced presentation of antigenic peptides by class I MHC
molecules, but not by class II molecules, which present peptides
generated in the endoplasmic reticulum and in endosomes, where TOP is
not expressed. Prevention of TOP expression by small interfering RNA
enhanced class I antigenic peptide presentation. York et al. (2003)
concluded that TOP is involved in degrading peptides released from the
proteasome and limits the extent of antigen presentation.
Norman et al. (2003) showed that NLN and thimet oligopeptidase (THOP1;
601117) have endopeptidase activity and demonstrated their presence in
ovine aortic and human umbilical vein endothelial cells. Both membrane
and soluble THOP1 catalyzed cleavage of bradykinin at the phe5-ser6
bond, although there were other kininases active at this peptide bond.
MAPPING
Using a cDNA encoding the rat Thop1 enzyme, Meckelein et al. (1996)
assigned the human THOP1 gene to chromosome 19 by hybridization to DNA
from human/rodent somatic cell hybrids. By fluorescence in situ
hybridization, they localized the gene to 19q13.3. However, after
localizing the THOP1 gene to the high-resolution cosmid contig map of
human chromosome 19, Torres et al. (1998) found that the FISH mapping to
19q13.3 by Meckelein et al. (1996) was incorrect. Results of the
hybridization and FISH mapping of positive clones indicated localization
of THOP1 to 19p13.3, thus excluding THOP1 as a candidate gene for AD2.
*FIELD* RF
1. Garrido, P. A. G.; Vandenbulcke, F.; Ramjaun, A. R.; Vincent, B.;
Checler, F.; Ferro, E.; Beaudet, A.: Confocal microscopy reveals
thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16)
in the classical secretory pathway. DNA Cell Biol. 18: 323-331,
1999.
2. Meckelein, B.; Rohan de Silva, H. A.; Roses, A. D.; Rao, P. N.;
Pettenati, M. J.; Xu, P.-T.; Hodge, R.; Glucksman, M. J.; Abraham,
C. R.: Human endopeptidase (THOP1) is localized on chromosome 19
within the linkage region for the late-onset Alzheimer disease AD2
locus. Genomics 31: 246-249, 1996.
3. Norman, M. U.; Reeve, S. B.; Dive, V.; Smith, A. I.; Lew, R. A.
: Regulation of cardiovascular signaling by kinins and products of
similar converting enzyme systems: endopeptidases 3.4.24.15 and 24.16
in endothelial cells: potential role in vasoactive peptide metabolism. Am.
J. Physiol. Heart Circ. Physiol. 284: H1978-H1984, 2003.
4. Papastoitsis, G.; Siman, R.; Scott, R.; Abraham, C. R.: Identification
of a metalloprotease from Alzheimer's disease brain able to degrade
the beta-amyloid precursor protein and generate amyloidogenic fragments. Biochemistry 33:
192-199, 1994.
5. Torres, M. P.; Prange, C.; Lennon, G.: Human endopeptidase 24.15
(THOP1) is localized on chromosome 19p13.3 and is excluded from the
linkage region for late-onset Alzheimer disease. Genomics 53: 239-240,
1998.
6. York, I. A.; Mo, A. X. Y.; Lemerise, K.; Zeng, W.; Shen, Y.; Abraham,
C. R.; Saric, T.; Goldberg, A. L.; Rock, K. L.: The cytosolic endopeptidase,
thimet oligopeptidase, destroys antigenic peptides and limits the
extent of MHC class I antigen presentation. Immunity 18: 429-440,
2003.
*FIELD* CN
Dorothy S. Reilly - updated: 10/15/2007
Paul J. Converse - updated: 1/12/2006
Carol A. Bocchini - updated: 12/9/1998
*FIELD* CD
Victor A. McKusick: 3/11/1996
*FIELD* ED
wwang: 10/15/2007
mgross: 1/12/2006
carol: 12/9/1998
terry: 12/9/1998
dkim: 12/7/1998
dkim: 9/11/1998
alopez: 7/30/1997
mark: 7/8/1997
mark: 3/18/1996
*RECORD*
*FIELD* NO
601117
*FIELD* TI
*601117 THIMET OLIGOPEPTIDASE 1; THOP1
;;TOP
*FIELD* TX
CLONING
Proteases involved in the amyloidogenic processing of amyloid precursor
read moreprotein (APP; 104760) represent likely candidates for the site of
mutation in a form of familial Alzheimer disease (AD2; 104310).
Formation of toxic amyloid in the brain parenchyma and cerebral
vasculature in Alzheimer disease requires the proteolytic release of the
39- to 43-amino acid amyloid beta peptide from its precursor, APP.
Papastoitsis et al. (1994) purified and characterized a metalloprotease
from human Alzheimer disease brain that was able to cleave a synthetic
peptide encompassing the amino-terminus of amyloid beta peptide and
generate amyloidogenic fragments from recombinant human APP. Sequence
comparison revealed that this enzyme, THOP1, has high homology to the
previously described rat metalloendopeptidase 24.15 (EC 3.4.24.15). The
beta-secretase-like activity of the human enzyme in vitro in combination
with its localization in neurons and its co-localization with APP in
transport vesicles purified from rabbit optic nerve rendered this enzyme
an interesting candidate for amyloidogenic processing of APP.
By immunocytochemical and Western blot analysis of mouse pituitary
corticotrophic cells, Garrido et al. (1999) observed a punctate
distribution and variable intense nuclear staining for endogenous Thop1.
Thop1 colocalized with syntaxin-6 (STX6; 603944) in the juxtanuclear
region and was found in small vesicular organelles throughout the cell
body, colocalizing with ACTH in some organelles.
GENE FUNCTION
Most antigenic peptides presented on major histocompatibility complex
(MHC) class I molecules are generated by proteasomes during protein
processing. To determine if cytosolic peptidases destroy these peptides,
York et al. (2003) overexpressed TOP in cells. They found that TOP
overexpression reduced presentation of antigenic peptides by class I MHC
molecules, but not by class II molecules, which present peptides
generated in the endoplasmic reticulum and in endosomes, where TOP is
not expressed. Prevention of TOP expression by small interfering RNA
enhanced class I antigenic peptide presentation. York et al. (2003)
concluded that TOP is involved in degrading peptides released from the
proteasome and limits the extent of antigen presentation.
Norman et al. (2003) showed that NLN and thimet oligopeptidase (THOP1;
601117) have endopeptidase activity and demonstrated their presence in
ovine aortic and human umbilical vein endothelial cells. Both membrane
and soluble THOP1 catalyzed cleavage of bradykinin at the phe5-ser6
bond, although there were other kininases active at this peptide bond.
MAPPING
Using a cDNA encoding the rat Thop1 enzyme, Meckelein et al. (1996)
assigned the human THOP1 gene to chromosome 19 by hybridization to DNA
from human/rodent somatic cell hybrids. By fluorescence in situ
hybridization, they localized the gene to 19q13.3. However, after
localizing the THOP1 gene to the high-resolution cosmid contig map of
human chromosome 19, Torres et al. (1998) found that the FISH mapping to
19q13.3 by Meckelein et al. (1996) was incorrect. Results of the
hybridization and FISH mapping of positive clones indicated localization
of THOP1 to 19p13.3, thus excluding THOP1 as a candidate gene for AD2.
*FIELD* RF
1. Garrido, P. A. G.; Vandenbulcke, F.; Ramjaun, A. R.; Vincent, B.;
Checler, F.; Ferro, E.; Beaudet, A.: Confocal microscopy reveals
thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16)
in the classical secretory pathway. DNA Cell Biol. 18: 323-331,
1999.
2. Meckelein, B.; Rohan de Silva, H. A.; Roses, A. D.; Rao, P. N.;
Pettenati, M. J.; Xu, P.-T.; Hodge, R.; Glucksman, M. J.; Abraham,
C. R.: Human endopeptidase (THOP1) is localized on chromosome 19
within the linkage region for the late-onset Alzheimer disease AD2
locus. Genomics 31: 246-249, 1996.
3. Norman, M. U.; Reeve, S. B.; Dive, V.; Smith, A. I.; Lew, R. A.
: Regulation of cardiovascular signaling by kinins and products of
similar converting enzyme systems: endopeptidases 3.4.24.15 and 24.16
in endothelial cells: potential role in vasoactive peptide metabolism. Am.
J. Physiol. Heart Circ. Physiol. 284: H1978-H1984, 2003.
4. Papastoitsis, G.; Siman, R.; Scott, R.; Abraham, C. R.: Identification
of a metalloprotease from Alzheimer's disease brain able to degrade
the beta-amyloid precursor protein and generate amyloidogenic fragments. Biochemistry 33:
192-199, 1994.
5. Torres, M. P.; Prange, C.; Lennon, G.: Human endopeptidase 24.15
(THOP1) is localized on chromosome 19p13.3 and is excluded from the
linkage region for late-onset Alzheimer disease. Genomics 53: 239-240,
1998.
6. York, I. A.; Mo, A. X. Y.; Lemerise, K.; Zeng, W.; Shen, Y.; Abraham,
C. R.; Saric, T.; Goldberg, A. L.; Rock, K. L.: The cytosolic endopeptidase,
thimet oligopeptidase, destroys antigenic peptides and limits the
extent of MHC class I antigen presentation. Immunity 18: 429-440,
2003.
*FIELD* CN
Dorothy S. Reilly - updated: 10/15/2007
Paul J. Converse - updated: 1/12/2006
Carol A. Bocchini - updated: 12/9/1998
*FIELD* CD
Victor A. McKusick: 3/11/1996
*FIELD* ED
wwang: 10/15/2007
mgross: 1/12/2006
carol: 12/9/1998
terry: 12/9/1998
dkim: 12/7/1998
dkim: 9/11/1998
alopez: 7/30/1997
mark: 7/8/1997
mark: 3/18/1996