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P52888

- THOP1_HUMAN

UniProt

P52888 - THOP1_HUMAN

Protein

Thimet oligopeptidase

Gene

THOP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation. Able to degrade the beta-amyloid precursor protein and generate amyloidogenic fragments.

    Catalytic activityi

    Preferential cleavage of bonds with hydrophobic residues at P1, P2 and P3' and a small residue at P1' in substrates of 5 to 15 residues.

    Cofactori

    Binds 1 zinc ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi473 – 4731Zinc; catalytic
    Active sitei474 – 4741
    Metal bindingi477 – 4771Zinc; catalytic
    Metal bindingi480 – 4801Zinc; catalytic

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. metalloendopeptidase activity Source: ProtInc
    3. peptide binding Source: Ensembl
    4. protein binding Source: IntAct

    GO - Biological processi

    1. peptide metabolic process Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM03.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thimet oligopeptidase (EC:3.4.24.15)
    Alternative name(s):
    Endopeptidase 24.15
    MP78
    Gene namesi
    Name:THOP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:11793. THOP1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA36505.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 689689Thimet oligopeptidasePRO_0000078153Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei257 – 2571N6-acetyllysine1 Publication
    Modified residuei278 – 2781PhosphotyrosineBy similarity
    Modified residuei538 – 5381N6-acetyllysine1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP52888.
    PaxDbiP52888.
    PeptideAtlasiP52888.
    PRIDEiP52888.

    PTM databases

    PhosphoSiteiP52888.

    Miscellaneous databases

    PMAP-CutDBP52888.

    Expressioni

    Gene expression databases

    ArrayExpressiP52888.
    BgeeiP52888.
    CleanExiHS_THOP1.
    GenevestigatoriP52888.

    Organism-specific databases

    HPAiCAB025497.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Calm3P621612EBI-372399,EBI-397530From a different organism.

    Protein-protein interaction databases

    BioGridi112921. 34 interactions.
    IntActiP52888. 3 interactions.
    MINTiMINT-3019782.
    STRINGi9606.ENSP00000304467.

    Structurei

    Secondary structure

    1
    689
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi30 – 5223
    Helixi56 – 583
    Turni61 – 644
    Helixi65 – 8319
    Helixi85 – 884
    Helixi92 – 11322
    Helixi116 – 12813
    Helixi136 – 15116
    Turni152 – 1554
    Helixi158 – 18427
    Beta strandi188 – 1914
    Turni193 – 1986
    Helixi201 – 2044
    Beta strandi207 – 2093
    Beta strandi215 – 2206
    Helixi221 – 23010
    Helixi234 – 24411
    Turni245 – 2484
    Helixi249 – 26921
    Helixi275 – 2806
    Helixi288 – 32437
    Turni334 – 3363
    Helixi337 – 34812
    Helixi353 – 3564
    Helixi357 – 3593
    Helixi362 – 37716
    Beta strandi379 – 3835
    Beta strandi395 – 4017
    Turni402 – 4043
    Beta strandi407 – 4148
    Beta strandi426 – 4316
    Beta strandi444 – 4496
    Helixi465 – 48319
    Helixi489 – 4913
    Turni498 – 5025
    Helixi503 – 5097
    Helixi510 – 5134
    Helixi515 – 5206
    Turni525 – 5273
    Helixi533 – 5419
    Helixi542 – 5443
    Helixi547 – 56418
    Helixi572 – 58211
    Helixi594 – 5974
    Helixi599 – 6024
    Turni606 – 6105
    Helixi611 – 63020
    Helixi635 – 64410
    Turni645 – 6484
    Helixi649 – 6513
    Helixi654 – 6629
    Helixi669 – 6746

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1S4BX-ray2.00P16-689[»]
    2O36X-ray1.95A16-688[»]
    ProteinModelPortaliP52888.
    SMRiP52888. Positions 24-677.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP52888.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M3 family.Curated

    Phylogenomic databases

    eggNOGiCOG0339.
    HOGENOMiHOG000245985.
    HOVERGENiHBG000238.
    InParanoidiP52888.
    KOiK01392.
    OMAiGCEPPAC.
    OrthoDBiEOG7SR4KW.
    PhylomeDBiP52888.
    TreeFamiTF300459.

    Family and domain databases

    Gene3Di1.10.1370.10. 2 hits.
    1.20.1050.40. 1 hit.
    3.40.390.10. 1 hit.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR024077. Neurolysin/TOP_dom2.
    IPR024080. Neurolysin/TOP_N.
    IPR001567. Pept_M3A_M3B.
    [Graphical view]
    PfamiPF01432. Peptidase_M3. 1 hit.
    [Graphical view]
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P52888-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MKPPAACAGD MADAASPCSV VNDLRWDLSA QQIEERTREL IEQTKRVYDQ    50
    VGTQEFEDVS YESTLKALAD VEVTYTVQRN ILDFPQHVSP SKDIRTASTE 100
    ADKKLSEFDV EMSMREDVYQ RIVWLQEKVQ KDSLRPEAAR YLERLIKLGR 150
    RNGLHLPRET QENIKRIKKK LSLLCIDFNK NLNEDTTFLP FTLQELGGLP 200
    EDFLNSLEKM EDGKLKVTLK YPHYFPLLKK CHVPETRRKV EEAFNCRCKE 250
    ENCAILKELV TLRAQKSRLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ 300
    KLKPLGEQER AVILELKRAE CERRGLPFDG RIRAWDMRYY MNQVEETRYC 350
    VDQNLLKEYF PVQVVTHGLL GIYQELLGLA FHHEEGASAW HEDVRLYTAR 400
    DAASGEVVGK FYLDLYPREG KYGHAACFGL QPGCLRQDGS RQIAIAAMVA 450
    NFTKPTADAP SLLQHDEVET YFHEFGHVMH QLCSQAEFAM FSGTHVERDF 500
    VEAPSQMLEN WVWEQEPLLR MSRHYRTGSA VPRELLEKLI ESRQANTGLF 550
    NLRQIVLAKV DQALHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH 600
    LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLNSKVGMD YRSCILRPGG 650
    SEDASAMLRR FLGRDPKQDA FLLSKGLQVG GCEPEPQVC 689
    Length:689
    Mass (Da):78,840
    Last modified:January 23, 2007 - v2
    Checksum:i092D53DD63B322DE
    GO
    Isoform 2 (identifier: P52888-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-489: Missing.
         636-636: K → KFPHYEVRPLRHVSLCLPLTWCDPGSGQPPESLTRNRWLPALRAGPALPGCNIALGSLQ

    Note: No experimental confirmation available.

    Show »
    Length:258
    Mass (Da):28,908
    Checksum:i6FCF592E0B1E2573
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 489489Missing in isoform 2. 1 PublicationVSP_056494Add
    BLAST
    Alternative sequencei636 – 6361K → KFPHYEVRPLRHVSLCLPLT WCDPGSGQPPESLTRNRWLP ALRAGPALPGCNIALGSLQ in isoform 2. 1 PublicationVSP_056495

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z50115 mRNA. Translation: CAA90477.1.
    U29366 mRNA. Translation: AAA82607.1.
    AK093392 mRNA. Translation: BAG52704.1.
    AC006538 Genomic DNA. Translation: AAD13118.1.
    BC000135 mRNA. Translation: AAH00135.1.
    BC002391 mRNA. Translation: AAH02391.1.
    CCDSiCCDS12095.1.
    PIRiJC4197. HYHUTH.
    RefSeqiNP_003240.1. NM_003249.3.
    UniGeneiHs.78769.

    Genome annotation databases

    EnsembliENST00000307741; ENSP00000304467; ENSG00000172009.
    ENST00000395212; ENSP00000378638; ENSG00000172009.
    GeneIDi7064.
    KEGGihsa:7064.
    UCSCiuc002lwj.3. human.

    Polymorphism databases

    DMDMi1708983.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z50115 mRNA. Translation: CAA90477.1 .
    U29366 mRNA. Translation: AAA82607.1 .
    AK093392 mRNA. Translation: BAG52704.1 .
    AC006538 Genomic DNA. Translation: AAD13118.1 .
    BC000135 mRNA. Translation: AAH00135.1 .
    BC002391 mRNA. Translation: AAH02391.1 .
    CCDSi CCDS12095.1.
    PIRi JC4197. HYHUTH.
    RefSeqi NP_003240.1. NM_003249.3.
    UniGenei Hs.78769.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1S4B X-ray 2.00 P 16-689 [» ]
    2O36 X-ray 1.95 A 16-688 [» ]
    ProteinModelPortali P52888.
    SMRi P52888. Positions 24-677.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112921. 34 interactions.
    IntActi P52888. 3 interactions.
    MINTi MINT-3019782.
    STRINGi 9606.ENSP00000304467.

    Protein family/group databases

    MEROPSi M03.001.

    PTM databases

    PhosphoSitei P52888.

    Polymorphism databases

    DMDMi 1708983.

    Proteomic databases

    MaxQBi P52888.
    PaxDbi P52888.
    PeptideAtlasi P52888.
    PRIDEi P52888.

    Protocols and materials databases

    DNASUi 7064.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000307741 ; ENSP00000304467 ; ENSG00000172009 .
    ENST00000395212 ; ENSP00000378638 ; ENSG00000172009 .
    GeneIDi 7064.
    KEGGi hsa:7064.
    UCSCi uc002lwj.3. human.

    Organism-specific databases

    CTDi 7064.
    GeneCardsi GC19P002785.
    HGNCi HGNC:11793. THOP1.
    HPAi CAB025497.
    MIMi 601117. gene.
    neXtProti NX_P52888.
    PharmGKBi PA36505.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0339.
    HOGENOMi HOG000245985.
    HOVERGENi HBG000238.
    InParanoidi P52888.
    KOi K01392.
    OMAi GCEPPAC.
    OrthoDBi EOG7SR4KW.
    PhylomeDBi P52888.
    TreeFami TF300459.

    Miscellaneous databases

    EvolutionaryTracei P52888.
    GeneWikii THOP1.
    GenomeRNAii 7064.
    NextBioi 27623.
    PMAP-CutDB P52888.
    PROi P52888.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P52888.
    Bgeei P52888.
    CleanExi HS_THOP1.
    Genevestigatori P52888.

    Family and domain databases

    Gene3Di 1.10.1370.10. 2 hits.
    1.20.1050.40. 1 hit.
    3.40.390.10. 1 hit.
    InterProi IPR024079. MetalloPept_cat_dom.
    IPR024077. Neurolysin/TOP_dom2.
    IPR024080. Neurolysin/TOP_N.
    IPR001567. Pept_M3A_M3B.
    [Graphical view ]
    Pfami PF01432. Peptidase_M3. 1 hit.
    [Graphical view ]
    PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and functional expression of a metalloendopeptidase from human brain with the ability to cleave a beta-APP substrate peptide."
      Thompson A., Huber G., Malherbe P.
      Biochem. Biophys. Res. Commun. 213:66-73(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. "cDNA cloning and gene structure of a human gene encoding a highly conserved metalloendopeptidase (EC 3.4.24.15)."
      Taylor G.R., Otulakowski G., Lau C.Y., Munroe D.G.
      Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Testis.
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lung and Placenta.
    6. "Identification of a metalloprotease from Alzheimer's disease brain able to degrade the beta-amyloid precursor protein and generate amyloidogenic fragments."
      Papastoitsis G., Siman R., Scott R., Abraham C.R.
      Biochemistry 33:192-199(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 67-78; 181-197 AND 199-200.
      Tissue: Brain.
    7. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-257 AND LYS-538, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase."
      Lim E.J., Sampath S., Coll-Rodriguez J., Schmidt J., Ray K., Rodgers D.W.
      J. Biol. Chem. 282:9722-9732(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 16-688, ZINC-BINDING SITES.

    Entry informationi

    Entry nameiTHOP1_HUMAN
    AccessioniPrimary (citable) accession number: P52888
    Secondary accession number(s): B3KSE2, Q9UCB3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 140 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3