P46076 (NPII_ASPOR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neutral protease 2
EC=3.4.24.39

Alternative name(s):
Deuterolysin
Neutral protease II
Short name=NPII

Gene names

ORF Names:

AO090010000493

Organism

Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold) [Complete proteome]

Taxonomic identifier

510516 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Pezizomycotina › leotiomyceta › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Trichocomaceae › mitosporic Trichocomaceae › Aspergillus › Aspergillus oryzae

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Metalloprotease that shows high activities on basic nuclear substrates such as histone and protamine.
Catalytic activity	Preferential cleavage of bonds with hydrophobic residues in P1'; also 3-Asn-|-Gln-4 and 8-Gly-|-Ser-9 bonds in insulin B chain.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Sequence similarities	Belongs to the peptidase M35 family.
Biophysicochemical properties	Temperature dependence: Thermostable.

Ontologies

Keywords
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Propeptide

20 – 175

156

PRO_0000029238

Chain

176 – 352

177

Neutral protease 2

PRO_0000029239

Sites

Active site

304

1

Metal binding

303

1

Zinc; catalytic

Metal binding

307

1

Zinc; catalytic

Metal binding

318

1

Zinc; catalytic

Amino acid modifications

Disulfide bond

181 ↔ 253

Ref.3

Disulfide bond

260 ↔ 278

Ref.3

Disulfide bond

292 ↔ 352

Ref.3

Experimental info

Mutagenesis

253

1

C → A: Optimal activity at 55 degrees Celsius; 10 degrees lower than wild-type. Ref.3

Sequence conflict

14

1

A → T in AAB19701. Ref.1

Sequence conflict

73

1

I → V in AAB19701. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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352

Helix Strand Turn

Details...

Beta strand

177 – 180

4

Helix

184 – 209

26

Helix

212 – 219

8

Helix

224 – 241

18

Beta strand

250 – 254

5

Beta strand

256 – 258

3

Beta strand

266 – 269

4

Helix

270 – 272

3

Beta strand

274 – 277

4

Helix

279 – 284

6

Helix

297 – 306

10

Turn

309 – 311

3

Beta strand

312 – 314

3

Helix

323 – 327

5

Helix

331 – 335

5

Helix

338 – 350

13

Sequences

	Sequence		Length	Mass (Da)
	P46076 [UniParc]. Last modified May 2, 2006. Version 2. Checksum: 53B75AF448E221C2	FASTA	352	37,502
	10 20 30 40 50 60 MRVTTLSTAL FALASTAVSA PTAGSSSPGL EVKLTQIDNT RVKAVVKNTG SEEVSFVHLN 70 80 90 100 110 120 FFKDAGPVKK VSIYRGQDEV QFEGIKRRLR SSGITKEAVT SLGAGETLED EFDIASTSDL 130 140 150 160 170 180 ASGGPVSIRS HGFVPIVVDG KITGYIPYKS NDLTVNVDGG KAAKVTKALS QLTRRTEVTD 190 200 210 220 230 240 CKGDAESSLT TALSNAAKLA NQAAEAAESG DESKFEEYFK TTDQQTRTTV AERLRAVAKE 250 260 270 280 290 300 AGSTSGGSTT YHCNDPYGYC EPNVLAYTLP SKNEIANCDI YYSELPPLAQ KCHAQDQATT 310 320 330 340 350 TLHEFTHAPG VYQPGTEDLG YGYDAATQLS AQDALNNADS YALYANAIEL KC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression in yeast of a cDNA clone encoding Aspergillus oryzae neutral protease II, a unique metalloprotease." Tatsumi H., Murakami S., Tsuji R.F., Ishida Y., Murakami K., Masaki A., Kawabe H., Arimura H., Nakano E., Motai H. Mol. Gen. Genet. 228:97-103(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 176-210; 279-281 AND 304-341. Strain: ATCC 20386 / 460.
[2]	"Genome sequencing and analysis of Aspergillus oryzae." Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K., Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H., Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E. , Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D., Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A., Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y., Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H., Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T., Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O., Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y., Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N., Kikuchi H. Nature 438:1157-1161(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 42149 / RIB 40.
[3]	"Elucidation of the thermal stability of the neutral proteinase II from Aspergillus oryzae." Tatsumi H., Ikegaya K., Murakami S., Kawabe H., Nakano E., Motai H. Biochim. Biophys. Acta 1208:179-185(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 176-352, DISULFIDE BONDS, MUTAGENESIS OF CYS-253.
[4]	"A quick solution: ab initio structure determination of a 19 kDa metalloproteinase using ACORN." McAuley K.E., Jia-Xing Y., Dodson E.J., Lehmbeck J., Ostergaard P.R., Wilson K.S. Acta Crystallogr. D 57:1571-1578(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 176-352.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S53810 mRNA. Translation: AAB19701.1.
AP007175 Genomic DNA. Translation: BAE66344.1.

PIR

S16547.

RefSeq

XP_001827477.1. XM_001827425.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EB6	X-ray	1.00	A	176-352	[»]

ProteinModelPortal

P46076.

SMR

P46076. Positions 176-352.

ModBase

Search...

Protein-protein interaction databases

STRING

5062.CADAORAP00004472.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

CADAORAT00004552; CADAORAP00004472; CADAORAG00004552.

GeneID

5999611.

KEGG

aor:AOR_1_818024.

Phylogenomic databases

eggNOG

NOG29258.

HOGENOM

HOG000193008.

OrthoDB

EOG4004TB.

Family and domain databases

Gene3D

3.40.390.10. 1 hit.

InterPro

IPR024079. MetalloPept_cat_dom.
IPR001384. Peptidase_M35.
[Graphical view]

Pfam

PF02102. Peptidase_M35. 1 hit.
[Graphical view]

PRINTS

PR00768. DEUTEROLYSIN.

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P46076.

Entry information

Entry name

NPII_ASPOR

Accession

Primary (citable) accession number: P46076
Secondary accession number(s): Q2TWM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	May 2, 2006
Last modified:	April 3, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program