NPII_ASPOR
ID NPII_ASPOR Reviewed; 352 AA.
AC P46076; Q2TWM9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Neutral protease 2;
DE EC=3.4.24.39;
DE AltName: Full=Deuterolysin;
DE AltName: Full=Neutral protease II;
DE Short=NPII;
DE Flags: Precursor;
GN ORFNames=AO090010000493;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 176-210; 279-281 AND
RP 304-341.
RC STRAIN=ATCC 20386 / 460;
RX PubMed=1886621; DOI=10.1007/bf00282453;
RA Tatsumi H., Murakami S., Tsuji R.F., Ishida Y., Murakami K., Masaki A.,
RA Kawabe H., Arimura H., Nakano E., Motai H.;
RT "Cloning and expression in yeast of a cDNA clone encoding Aspergillus
RT oryzae neutral protease II, a unique metalloprotease.";
RL Mol. Gen. Genet. 228:97-103(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [3]
RP PROTEIN SEQUENCE OF 176-352, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-253.
RX PubMed=8086433; DOI=10.1016/0167-4838(94)90176-7;
RA Tatsumi H., Ikegaya K., Murakami S., Kawabe H., Nakano E., Motai H.;
RT "Elucidation of the thermal stability of the neutral proteinase II from
RT Aspergillus oryzae.";
RL Biochim. Biophys. Acta 1208:179-185(1994).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 176-352 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVE SITE.
RX PubMed=11679721; DOI=10.1107/s090744490101335x;
RA McAuley K.E., Jia-Xing Y., Dodson E.J., Lehmbeck J., Ostergaard P.R.,
RA Wilson K.S.;
RT "A quick solution: ab initio structure determination of a 19 kDa
RT metalloproteinase using ACORN.";
RL Acta Crystallogr. D 57:1571-1578(2001).
CC -!- FUNCTION: Metalloprotease that shows high activities on basic nuclear
CC substrates such as histone and protamine.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage of bonds with hydrophobic residues in
CC P1'. Also 3-Asn-|-Gln-4 and 8-Gly-|-Ser-9 bonds in insulin B chain.;
CC EC=3.4.24.39;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11679721};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:11679721};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable.;
CC -!- SIMILARITY: Belongs to the peptidase M35 family. {ECO:0000305}.
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DR EMBL; S53810; AAB19701.1; -; mRNA.
DR EMBL; AP007175; BAE66344.1; -; Genomic_DNA.
DR PIR; S16547; S16547.
DR RefSeq; XP_001827477.1; XM_001827425.2.
DR PDB; 1EB6; X-ray; 1.00 A; A=176-352.
DR PDBsum; 1EB6; -.
DR AlphaFoldDB; P46076; -.
DR SMR; P46076; -.
DR MEROPS; M35.002; -.
DR EnsemblFungi; BAE66344; BAE66344; AO090010000493.
DR GeneID; 5999611; -.
DR KEGG; aor:AO090010000493; -.
DR VEuPathDB; FungiDB:AO090010000493; -.
DR HOGENOM; CLU_039313_1_1_1; -.
DR OMA; NTIMDEH; -.
DR BRENDA; 3.4.24.39; 522.
DR EvolutionaryTrace; P46076; -.
DR Proteomes; UP000006564; Chromosome 8.
DR GO; GO:0005576; C:extracellular region; IDA:AspGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001384; Peptidase_M35.
DR Pfam; PF02102; Peptidase_M35; 1.
DR PRINTS; PR00768; DEUTEROLYSIN.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Zinc; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..175
FT /evidence="ECO:0000269|PubMed:1886621,
FT ECO:0000269|PubMed:8086433"
FT /id="PRO_0000029238"
FT CHAIN 176..352
FT /note="Neutral protease 2"
FT /id="PRO_0000029239"
FT ACT_SITE 304
FT /evidence="ECO:0000269|PubMed:11679721"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11679721,
FT ECO:0007744|PDB:1EB6"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11679721,
FT ECO:0007744|PDB:1EB6"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11679721,
FT ECO:0007744|PDB:1EB6"
FT DISULFID 181..253
FT /evidence="ECO:0000269|PubMed:8086433"
FT DISULFID 260..278
FT /evidence="ECO:0000269|PubMed:8086433"
FT DISULFID 292..352
FT /evidence="ECO:0000269|PubMed:8086433"
FT MUTAGEN 253
FT /note="C->A: Optimal activity at 55 degrees Celsius; 10
FT degrees lower than wild-type."
FT /evidence="ECO:0000269|PubMed:8086433"
FT CONFLICT 14
FT /note="A -> T (in Ref. 1; AAB19701)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="I -> V (in Ref. 1; AAB19701)"
FT /evidence="ECO:0000305"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 184..209
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 212..219
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 224..241
FT /evidence="ECO:0007829|PDB:1EB6"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:1EB6"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1EB6"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:1EB6"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 279..284
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 297..306
FT /evidence="ECO:0007829|PDB:1EB6"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:1EB6"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 323..327
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 331..335
FT /evidence="ECO:0007829|PDB:1EB6"
FT HELIX 338..350
FT /evidence="ECO:0007829|PDB:1EB6"
SQ SEQUENCE 352 AA; 37502 MW; 53B75AF448E221C2 CRC64;
MRVTTLSTAL FALASTAVSA PTAGSSSPGL EVKLTQIDNT RVKAVVKNTG SEEVSFVHLN
FFKDAGPVKK VSIYRGQDEV QFEGIKRRLR SSGITKEAVT SLGAGETLED EFDIASTSDL
ASGGPVSIRS HGFVPIVVDG KITGYIPYKS NDLTVNVDGG KAAKVTKALS QLTRRTEVTD
CKGDAESSLT TALSNAAKLA NQAAEAAESG DESKFEEYFK TTDQQTRTTV AERLRAVAKE
AGSTSGGSTT YHCNDPYGYC EPNVLAYTLP SKNEIANCDI YYSELPPLAQ KCHAQDQATT
TLHEFTHAPG VYQPGTEDLG YGYDAATQLS AQDALNNADS YALYANAIEL KC
