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Protein

Thimet oligopeptidase

Gene

THOP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi473Zinc; catalytic1
Active sitei4741
Metal bindingi477Zinc; catalytic1
Metal bindingi480Zinc; catalytic1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: ProtInc
  • peptide binding Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS10433-MONOMER.
SIGNORiP52888.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11793. THOP1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi7064.
OpenTargetsiENSG00000172009.
PharmGKBiPA36505.

Polymorphism and mutation databases

BioMutaiTHOP1.
DMDMi1708983.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000781531 – 689Thimet oligopeptidaseAdd BLAST689

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16PhosphoserineCombined sources1
Modified residuei172PhosphoserineBy similarity1
Modified residuei257N6-acetyllysineCombined sources1
Modified residuei278PhosphotyrosineBy similarity1
Modified residuei538N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP52888.
MaxQBiP52888.
PaxDbiP52888.
PeptideAtlasiP52888.
PRIDEiP52888.

PTM databases

iPTMnetiP52888.
PhosphoSitePlusiP52888.

Miscellaneous databases

PMAP-CutDBP52888.

Expressioni

Gene expression databases

BgeeiENSG00000172009.
CleanExiHS_THOP1.
ExpressionAtlasiP52888. baseline and differential.
GenevisibleiP52888. HS.

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. 38 interactors.
IntActiP52888. 4 interactors.
MINTiMINT-3019782.
STRINGi9606.ENSP00000304467.

Structurei

Secondary structure

1689
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 52Combined sources23
Helixi56 – 58Combined sources3
Turni61 – 64Combined sources4
Helixi65 – 83Combined sources19
Helixi85 – 88Combined sources4
Helixi92 – 113Combined sources22
Helixi116 – 128Combined sources13
Helixi136 – 151Combined sources16
Turni152 – 155Combined sources4
Helixi158 – 184Combined sources27
Beta strandi188 – 191Combined sources4
Turni193 – 198Combined sources6
Helixi201 – 204Combined sources4
Beta strandi207 – 209Combined sources3
Beta strandi215 – 220Combined sources6
Helixi221 – 230Combined sources10
Helixi234 – 244Combined sources11
Turni245 – 248Combined sources4
Helixi249 – 269Combined sources21
Helixi275 – 280Combined sources6
Helixi288 – 324Combined sources37
Turni334 – 336Combined sources3
Helixi337 – 348Combined sources12
Helixi353 – 356Combined sources4
Helixi357 – 359Combined sources3
Helixi362 – 377Combined sources16
Beta strandi379 – 383Combined sources5
Beta strandi395 – 401Combined sources7
Turni402 – 404Combined sources3
Beta strandi407 – 414Combined sources8
Beta strandi426 – 431Combined sources6
Beta strandi444 – 449Combined sources6
Helixi465 – 483Combined sources19
Helixi489 – 491Combined sources3
Turni498 – 502Combined sources5
Helixi503 – 509Combined sources7
Helixi510 – 513Combined sources4
Helixi515 – 520Combined sources6
Turni525 – 527Combined sources3
Helixi533 – 541Combined sources9
Helixi542 – 544Combined sources3
Helixi547 – 564Combined sources18
Helixi572 – 582Combined sources11
Helixi594 – 597Combined sources4
Helixi599 – 602Combined sources4
Turni606 – 610Combined sources5
Helixi611 – 630Combined sources20
Helixi635 – 644Combined sources10
Turni645 – 648Combined sources4
Helixi649 – 651Combined sources3
Helixi654 – 662Combined sources9
Helixi669 – 674Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S4BX-ray2.00P16-689[»]
2O36X-ray1.95A16-688[»]
ProteinModelPortaliP52888.
SMRiP52888.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52888.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M3 family.Curated

Phylogenomic databases

eggNOGiKOG2089. Eukaryota.
COG0339. LUCA.
GeneTreeiENSGT00550000074738.
HOGENOMiHOG000245985.
HOVERGENiHBG000238.
InParanoidiP52888.
KOiK01392.
OMAiSYTVQRN.
OrthoDBiEOG091G0325.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564941 – 489Missing in isoform 2. 1 PublicationAdd BLAST489
Alternative sequenceiVSP_056495636K → KFPHYEVRPLRHVSLCLPLT WCDPGSGQPPESLTRNRWLP ALRAGPALPGCNIALGSLQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_003249.4. [P52888-1]
UniGeneiHs.78769.

Genome annotation databases

EnsembliENST00000307741; ENSP00000304467; ENSG00000172009. [P52888-1]
ENST00000395212; ENSP00000378638; ENSG00000172009. [P52888-2]
GeneIDi7064.
KEGGihsa:7064.
UCSCiuc002lwj.4. human. [P52888-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_003249.4. [P52888-1]
UniGeneiHs.78769.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S4BX-ray2.00P16-689[»]
2O36X-ray1.95A16-688[»]
ProteinModelPortaliP52888.
SMRiP52888.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112921. 38 interactors.
IntActiP52888. 4 interactors.
MINTiMINT-3019782.
STRINGi9606.ENSP00000304467.

Protein family/group databases

MEROPSiM03.001.

PTM databases

iPTMnetiP52888.
PhosphoSitePlusiP52888.

Polymorphism and mutation databases

BioMutaiTHOP1.
DMDMi1708983.

Proteomic databases

EPDiP52888.
MaxQBiP52888.
PaxDbiP52888.
PeptideAtlasiP52888.
PRIDEiP52888.

Protocols and materials databases

DNASUi7064.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307741; ENSP00000304467; ENSG00000172009. [P52888-1]
ENST00000395212; ENSP00000378638; ENSG00000172009. [P52888-2]
GeneIDi7064.
KEGGihsa:7064.
UCSCiuc002lwj.4. human. [P52888-1]

Organism-specific databases

CTDi7064.
DisGeNETi7064.
GeneCardsiTHOP1.
HGNCiHGNC:11793. THOP1.
HPAiCAB025497.
MIMi601117. gene.
neXtProtiNX_P52888.
OpenTargetsiENSG00000172009.
PharmGKBiPA36505.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2089. Eukaryota.
COG0339. LUCA.
GeneTreeiENSGT00550000074738.
HOGENOMiHOG000245985.
HOVERGENiHBG000238.
InParanoidiP52888.
KOiK01392.
OMAiSYTVQRN.
OrthoDBiEOG091G0325.
PhylomeDBiP52888.
TreeFamiTF300459.

Enzyme and pathway databases

BioCyciZFISH:HS10433-MONOMER.
SIGNORiP52888.

Miscellaneous databases

ChiTaRSiTHOP1. human.
EvolutionaryTraceiP52888.
GeneWikiiTHOP1.
GenomeRNAii7064.
PMAP-CutDBP52888.
PROiP52888.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172009.
CleanExiHS_THOP1.
ExpressionAtlasiP52888. baseline and differential.
GenevisibleiP52888. HS.

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]
ProtoNetiSearch...

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: November 2, 2016
This is version 161 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.