O59196 (TET_PYRHO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tetrahedral aminopeptidase
Short name=TET
Short name=TET aminopeptidase
EC=3.4.11.-

Alternative name(s):
Leucyl aminopeptidase
PhTET2

Gene names

Name:	frvX
Ordered Locus Names:	PH1527

Organism

Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3) [Complete proteome] [HAMAP]

Taxonomic identifier

70601 [NCBI]

Taxonomic lineage

Archaea › Euryarchaeota › Thermococci › Thermococcales › Thermococcaceae › Pyrococcus

Protein attributes

Sequence length	353 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as an aminopeptidase, with a clear preference for leucine as the N-terminal amino acid. However, can also cleave moderately long polypeptide substrates of various compositions in a fairly unspecific manner. Has neither carboxypeptidase nor endoproteolytic activities, and it is devoid of N-terminal deblocking activity. Is involved in protein degradation, performing degradation of oligopeptides produced by the proteasome into single amino acids. Ref.2 Ref.3 Ref.4
Cofactor	Binds 2 Zn2+ ions per subunit. Can also use Co2+. Ref.2 Ref.3 Ref.4
Enzyme regulation	Inhibited by EDTA and bestatin in vitro. Is insensitive to papain, antipain, chymostatin, leupeptin, pepstatin and aprotinin. Ref.2
Subunit structure	Homododecamer. The assembly of six dimers results in a tetrahedral-shaped structure; all 12 active sites are located on the inside of the tetrahedron. Substrate access is granted by four pores with a maximal diameter of 18 Angstroms, allowing only small peptides and unfolded proteins access to the active site. Beside the four entry ports, TET contains 12 small product release openings, which are large enough to allow passage of only single amino acid residues. Ref.2 Ref.3 Ref.4
Miscellaneous	The hydrolytic mechanism is nonprocessive. Therefore, the enzyme does not process one substrate molecule completely before starting with another one. Instead, the reaction products are generated by multiple rounds of substrate digestion.
Sequence similarities	Belongs to the peptidase M42 family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.5 with Leu-pNA as substrate. Strong activity is still detectable at pH 6 and 9. Ref.2 Temperature dependence: Optimum temperature is 100 degrees Celsius over a broad pH array. At temperatures lower than 70 degrees Celsius, less than 10% of the maximum activity is detected. Highly thermostable. Shows half-lives of 24.8 minutes and 10.03 hours when incubated at 100 and 80 degrees Celsius, respectively.

Ontologies

Keywords
Ligand	Cobalt Metal-binding Zinc
Molecular function	Aminopeptidase Hydrolase Metalloprotease Protease
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	aminopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 353

353

Tetrahedral aminopeptidase

PRO_0000391012

Sites

Active site

212

1

Proton acceptor Ref.3 Ref.4

Metal binding

68

1

Zinc 1

Metal binding

182

1

Zinc 1

Metal binding

182

1

Zinc 2

Metal binding

213

1

Zinc 2

Metal binding

235

1

Zinc 1

Metal binding

323

1

Zinc 2

Secondary structure

1

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353

Helix Strand Turn

Details...

Helix

9 – 17

9

Helix

30 – 37

8

Helix

38 – 40

3

Beta strand

41 – 46

6

Beta strand

52 – 56

5

Beta strand

62 – 68

7

Beta strand

75 – 79

5

Beta strand

85 – 88

4

Helix

95 – 97

3

Turn

98 – 100

3

Beta strand

103 – 107

5

Helix

136 – 138

3

Helix

148 – 153

6

Beta strand

161 – 164

4

Beta strand

169 – 171

3

Beta strand

175 – 178

4

Helix

181 – 196

16

Beta strand

201 – 210

10

Helix

220 – 223

4

Beta strand

232 – 238

7

Helix

247 – 249

3

Beta strand

259 – 264

6

Helix

271 – 283

13

Beta strand

289 – 292

4

Helix

303 – 305

3

Beta strand

315 – 321

7

Beta strand

323 – 325

3

Beta strand

327 – 330

4

Helix

331 – 347

17

Helix

348 – 350

3

Sequences

	Sequence		Length	Mass (Da)
	O59196 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: A6AE25809C8B2041	FASTA	353	39,014
	10 20 30 40 50 60 MEVRNMVDYE LLKKVVEAPG VSGYEFLGIR DVVIEEIKDY VDEVKVDKLG NVIAHKKGEG 70 80 90 100 110 120 PKVMIAAHMD QIGLMVTHIE KNGFLRVAPI GGVDPKTLIA QRFKVWIDKG KFIYGVGASV 130 140 150 160 170 180 PPHIQKPEDR KKAPDWDQIF IDIGAESKEE AEDMGVKIGT VITWDGRLER LGKHRFVSIA 190 200 210 220 230 240 FDDRIAVYTI LEVAKQLKDA KADVYFVATV QEEVGLRGAR TSAFGIEPDY GFAIDVTIAA 250 260 270 280 290 300 DIPGTPEHKQ VTHLGKGTAI KIMDRSVICH PTIVRWLEEL AKKHEIPYQL EILLGGGTDA 310 320 330 340 350 GAIHLTKAGV PTGALSVPAR YIHSNTEVVD ERDVDATVEL MTKALENIHE LKI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3." Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S., Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K., Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T. , Tanaka T., Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T., Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H. DNA Res. 5:55-76(1998) [PubMed: 9679194] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3.
[2]	"Characterization of a TET-like aminopeptidase complex from the hyperthermophilic archaeon Pyrococcus horikoshii." Dura M.A., Receveur-Brechot V., Andrieu J.P., Ebel C., Schoehn G., Roussel A., Franzetti B. Biochemistry 44:3477-3486(2005) [PubMed: 15736957] [Abstract] Cited for: FUNCTION AS AN AMINOPEPTIDASE, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, REACTION MECHANISM.
[3]	"Crystal structure of a dodecameric tetrahedral-shaped aminopeptidase." Russo S., Baumann U. J. Biol. Chem. 279:51275-51281(2004) [PubMed: 15375159] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH ZINC IONS, FUNCTION AS AN AMINOPEPTIDASE, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, ACTIVE SITE, CATALYTIC MECHANISM.
[4]	"Crystal structure of TET protease reveals complementary protein degradation pathways in prokaryotes." Borissenko L., Groll M. J. Mol. Biol. 346:1207-1219(2005) [PubMed: 15713475] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEXES WITH ZINC IONS AND THE INHIBITOR AMASTATIN, FUNCTION IN PROTEIN DEGRADATION, COFACTOR, SUBUNIT, ACTIVE SITE, CATALYTIC MECHANISM.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BA000001 Genomic DNA. Translation: BAA30637.1.

PIR

E71029.

RefSeq

NP_143387.1. NC_000961.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XFO	X-ray	1.96	A/B/C/D	1-353	[»]
1Y0R	X-ray	1.75	A	1-353	[»]
1Y0Y	X-ray	1.60	A	1-353	[»]

ProteinModelPortal

O59196.

SMR

O59196. Positions 1-353.

ModBase

Search...

Protein family/group databases

MEROPS

M42.004.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBPYRT00000001406; EBPYRP00000001406; EBPYRG00000001406.

GeneID

1443843.

GenomeReviews

Gene locus PH1527 in contig BA000001_GR.

KEGG

pho:PH1527.

NMPDR

fig|70601.1.peg.1496.

Organism-specific databases

CMR

Search...

Phylogenomic databases

GeneTree

EBGT00050000022566.

HOGENOM

HBG426188.

OMA

HPTIVRW.

PhylomeDB

O59196.

ProtClustDB

CLSK253326.

Enzyme and pathway databases

BioCyc

PHOR70601:PH1527-MONOMER.

Family and domain databases

InterPro

IPR008007. Peptidase_M42.
IPR023367. Peptidase_M42_dom2.
[Graphical view]

Gene3D

G3DSA:2.40.30.40. G3DSA:2.40.30.40. 1 hit.

KO

K01179.

Pfam

PF05343. Peptidase_M42. 1 hit.
[Graphical view]

PIRSF

PIRSF001123. PepA_GA. 1 hit.

ProtoNet

Search...

Entry information

Entry name

TET_PYRHO

Accession

Primary (citable) accession number: O59196

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 9, 2010
Last sequence update:	August 1, 1998
Last modified:	December 14, 2011
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program