P52888 (THOP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thimet oligopeptidase
EC=3.4.24.15

Alternative name(s):
Endopeptidase 24.15
MP78

Gene names

Name:

THOP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	689 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 activity	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.
Cofactor	Binds 1 zinc ion per subunit.
Subunit structure	Monomer By similarity.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase M3 family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara peptide metabolic process Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Traceable author statement Ref.1. Source: ProtInc peptide binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 689

689

Thimet oligopeptidase

PRO_0000078153

Sites

Active site

474

1

Metal binding

473

1

Zinc; catalytic

Metal binding

477

1

Zinc; catalytic

Metal binding

480

1

Zinc; catalytic

Amino acid modifications

Modified residue

257

1

N6-acetyllysine Ref.6

Modified residue

278

1

Phosphotyrosine By similarity

Modified residue

538

1

N6-acetyllysine Ref.6

Secondary structure

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689

Helix Strand Turn

Details...

Helix

30 – 52

23

Helix

56 – 58

3

Turn

61 – 64

4

Helix

65 – 83

19

Helix

85 – 88

4

Helix

92 – 113

22

Helix

116 – 128

13

Helix

136 – 151

16

Turn

152 – 155

4

Helix

158 – 184

27

Beta strand

188 – 191

4

Turn

193 – 198

6

Helix

201 – 204

4

Beta strand

207 – 209

3

Beta strand

215 – 220

6

Helix

221 – 230

10

Helix

234 – 244

11

Turn

245 – 248

4

Helix

249 – 269

21

Helix

275 – 280

6

Helix

288 – 324

37

Turn

334 – 336

3

Helix

337 – 348

12

Helix

353 – 356

4

Helix

357 – 359

3

Helix

362 – 377

16

Beta strand

379 – 383

5

Beta strand

395 – 401

7

Turn

402 – 404

3

Beta strand

407 – 414

8

Beta strand

426 – 431

6

Beta strand

444 – 449

6

Helix

465 – 483

19

Helix

489 – 491

3

Turn

498 – 502

5

Helix

503 – 509

7

Helix

510 – 513

4

Helix

515 – 520

6

Turn

525 – 527

3

Helix

533 – 541

9

Helix

542 – 544

3

Helix

547 – 564

18

Helix

572 – 582

11

Helix

594 – 597

4

Helix

599 – 602

4

Turn

606 – 610

5

Helix

611 – 630

20

Helix

635 – 644

10

Turn

645 – 648

4

Helix

649 – 651

3

Helix

654 – 662

9

Helix

669 – 674

6

Sequences

	Sequence		Length	Mass (Da)
	P52888 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 092D53DD63B322DE	FASTA	689	78,840
	10 20 30 40 50 60 MKPPAACAGD MADAASPCSV VNDLRWDLSA QQIEERTREL IEQTKRVYDQ VGTQEFEDVS 70 80 90 100 110 120 YESTLKALAD VEVTYTVQRN ILDFPQHVSP SKDIRTASTE ADKKLSEFDV EMSMREDVYQ 130 140 150 160 170 180 RIVWLQEKVQ KDSLRPEAAR YLERLIKLGR RNGLHLPRET QENIKRIKKK LSLLCIDFNK 190 200 210 220 230 240 NLNEDTTFLP FTLQELGGLP EDFLNSLEKM EDGKLKVTLK YPHYFPLLKK CHVPETRRKV 250 260 270 280 290 300 EEAFNCRCKE ENCAILKELV TLRAQKSRLL GFHTHADYVL EMNMAKTSQT VATFLDELAQ 310 320 330 340 350 360 KLKPLGEQER AVILELKRAE CERRGLPFDG RIRAWDMRYY MNQVEETRYC VDQNLLKEYF 370 380 390 400 410 420 PVQVVTHGLL GIYQELLGLA FHHEEGASAW HEDVRLYTAR DAASGEVVGK FYLDLYPREG 430 440 450 460 470 480 KYGHAACFGL QPGCLRQDGS RQIAIAAMVA NFTKPTADAP SLLQHDEVET YFHEFGHVMH 490 500 510 520 530 540 QLCSQAEFAM FSGTHVERDF VEAPSQMLEN WVWEQEPLLR MSRHYRTGSA VPRELLEKLI 550 560 570 580 590 600 ESRQANTGLF NLRQIVLAKV DQALHTQTDA DPAEEYARLC QEILGVPATP GTNMPATFGH 610 620 630 640 650 660 LAGGYDAQYY GYLWSEVYSM DMFHTRFKQE GVLNSKVGMD YRSCILRPGG SEDASAMLRR 670 680 FLGRDPKQDA FLLSKGLQVG GCEPEPQVC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]. 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].
[3]	"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].
[4]	"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]. Tissue: Lung and Placenta.
[5]	"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.
[6]	"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, MASS SPECTROMETRY.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z50115 mRNA. Translation: CAA90477.1.
U29366 mRNA. Translation: AAA82607.1.
AC006538 Genomic DNA. Translation: AAD13118.1.
BC000135 mRNA. Translation: AAH00135.1.
BC002391 mRNA. Translation: AAH02391.1.

IPI

IPI00549189.

PIR

HYHUTH. JC4197.

RefSeq

NP_003240.1. NM_003249.3.

UniGene

Hs.78769.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S4B	X-ray	2.00	P	16-688	[»]
2O36	X-ray	1.95	A	16-688	[»]

ProteinModelPortal

P52888.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52888. 1 interaction.

MINT

MINT-3019782.

STRING

9606.ENSP00000304467.

Protein family/group databases

MEROPS

M03.001.

PTM databases

PhosphoSite

P52888.

Polymorphism databases

DMDM

1708983.

Proteomic databases

PaxDb

P52888.

PeptideAtlas

P52888.

PRIDE

P52888.

Protocols and materials databases

DNASU

7064.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000307741; ENSP00000304467; ENSG00000172009.

GeneID

7064.

KEGG

hsa:7064.

UCSC

uc002lwj.3. human.

Organism-specific databases

CTD

7064.

GeneCards

GC19P002785.

HGNC

HGNC:11793. THOP1.

HPA

CAB025497.

MIM

601117. gene.

neXtProt

NX_P52888.

PharmGKB

PA36505.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0339.

HOGENOM

HOG000245985.

HOVERGEN

HBG000238.

InParanoid

P52888.

KO

K01392.

OMA

ITFKERT.

OrthoDB

EOG4CG07P.

PhylomeDB

P52888.

Gene expression databases

ArrayExpress

P52888.

Bgee

P52888.

CleanEx

HS_THOP1.

Genevestigator

P52888.

GermOnline

ENSG00000172009. Homo sapiens.

Family and domain databases

Gene3D

1.10.1370.10. 2 hits.
1.20.1050.40. 1 hit.
3.40.390.10. 1 hit.

InterPro

IPR024079. MetalloPept_cat_dom.
IPR024077. Neurolysin/TOP_dom2.
IPR024080. Neurolysin/TOP_N.
IPR001567. Pept_M3A_M3B.
[Graphical view]

Pfam

PF01432. Peptidase_M3. 1 hit.
[Graphical view]

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P52888.

GenomeRNAi

7064.

NextBio

27623.

PMAP-CutDB

P52888.

SOURCE

Search...

Entry information

Entry name

THOP1_HUMAN

Accession

Primary (citable) accession number: P52888
Secondary accession number(s): Q9UCB3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.