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P52888

- THOP1_HUMAN

UniProt

P52888 - THOP1_HUMAN

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Protein

Thimet oligopeptidase

Gene

THOP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

GO - Biological processi

  1. intracellular signal transduction Source: Ensembl
  2. peptide metabolic process Source: Ensembl
Complete GO annotation...

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-KW
Complete GO annotation...

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

BgeeiP52888.
CleanExiHS_THOP1.
ExpressionAtlasiP52888. baseline and differential.
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 – 5223Combined sources
Helixi56 – 583Combined sources
Turni61 – 644Combined sources
Helixi65 – 8319Combined sources
Helixi85 – 884Combined sources
Helixi92 – 11322Combined sources
Helixi116 – 12813Combined sources
Helixi136 – 15116Combined sources
Turni152 – 1554Combined sources
Helixi158 – 18427Combined sources
Beta strandi188 – 1914Combined sources
Turni193 – 1986Combined sources
Helixi201 – 2044Combined sources
Beta strandi207 – 2093Combined sources
Beta strandi215 – 2206Combined sources
Helixi221 – 23010Combined sources
Helixi234 – 24411Combined sources
Turni245 – 2484Combined sources
Helixi249 – 26921Combined sources
Helixi275 – 2806Combined sources
Helixi288 – 32437Combined sources
Turni334 – 3363Combined sources
Helixi337 – 34812Combined sources
Helixi353 – 3564Combined sources
Helixi357 – 3593Combined sources
Helixi362 – 37716Combined sources
Beta strandi379 – 3835Combined sources
Beta strandi395 – 4017Combined sources
Turni402 – 4043Combined sources
Beta strandi407 – 4148Combined sources
Beta strandi426 – 4316Combined sources
Beta strandi444 – 4496Combined sources
Helixi465 – 48319Combined sources
Helixi489 – 4913Combined sources
Turni498 – 5025Combined sources
Helixi503 – 5097Combined sources
Helixi510 – 5134Combined sources
Helixi515 – 5206Combined sources
Turni525 – 5273Combined sources
Helixi533 – 5419Combined sources
Helixi542 – 5443Combined sources
Helixi547 – 56418Combined sources
Helixi572 – 58211Combined sources
Helixi594 – 5974Combined sources
Helixi599 – 6024Combined sources
Turni606 – 6105Combined sources
Helixi611 – 63020Combined sources
Helixi635 – 64410Combined sources
Turni645 – 6484Combined sources
Helixi649 – 6513Combined sources
Helixi654 – 6629Combined sources
Helixi669 – 6746Combined sources

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.
GeneTreeiENSGT00550000074738.
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. 2 hits.
[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

        10         20         30         40         50
MKPPAACAGD MADAASPCSV VNDLRWDLSA QQIEERTREL IEQTKRVYDQ
60 70 80 90 100
VGTQEFEDVS YESTLKALAD VEVTYTVQRN ILDFPQHVSP SKDIRTASTE
110 120 130 140 150
ADKKLSEFDV EMSMREDVYQ RIVWLQEKVQ KDSLRPEAAR YLERLIKLGR
160 170 180 190 200
RNGLHLPRET QENIKRIKKK LSLLCIDFNK NLNEDTTFLP FTLQELGGLP
210 220 230 240 250
EDFLNSLEKM EDGKLKVTLK YPHYFPLLKK CHVPETRRKV EEAFNCRCKE
260 270 280 290 300
ENCAILKELV TLRAQKSRLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ
310 320 330 340 350
KLKPLGEQER AVILELKRAE CERRGLPFDG RIRAWDMRYY MNQVEETRYC
360 370 380 390 400
VDQNLLKEYF PVQVVTHGLL GIYQELLGLA FHHEEGASAW HEDVRLYTAR
410 420 430 440 450
DAASGEVVGK FYLDLYPREG KYGHAACFGL QPGCLRQDGS RQIAIAAMVA
460 470 480 490 500
NFTKPTADAP SLLQHDEVET YFHEFGHVMH QLCSQAEFAM FSGTHVERDF
510 520 530 540 550
VEAPSQMLEN WVWEQEPLLR MSRHYRTGSA VPRELLEKLI ESRQANTGLF
560 570 580 590 600
NLRQIVLAKV DQALHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH
610 620 630 640 650
LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLNSKVGMD YRSCILRPGG
660 670 680
SEDASAMLRR FLGRDPKQDA FLLSKGLQVG GCEPEPQVC
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. [P52888-1]
PIRiJC4197. HYHUTH.
RefSeqiNP_003240.1. NM_003249.3.
UniGeneiHs.78769.

Genome annotation databases

EnsembliENST00000307741; ENSP00000304467; ENSG00000172009. [P52888-1]
ENST00000395212; ENSP00000378638; ENSG00000172009. [P52888-2]
GeneIDi7064.
KEGGihsa:7064.
UCSCiuc002lwj.3. human. [P52888-1]

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. [P52888-1 ]
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 . [P52888-1 ]
ENST00000395212 ; ENSP00000378638 ; ENSG00000172009 . [P52888-2 ]
GeneIDi 7064.
KEGGi hsa:7064.
UCSCi uc002lwj.3. human. [P52888-1 ]

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.
GeneTreei ENSGT00550000074738.
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

Bgeei P52888.
CleanExi HS_THOP1.
ExpressionAtlasi P52888. baseline and differential.
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. 2 hits.
[Graphical view ]
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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 29, 2014
This is version 141 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