ID   MEP3_COCP7              Reviewed;         354 AA.
AC   C5P507; Q3KRR0;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-SEP-2009, sequence version 1.
DT   03-AUG-2022, entry version 53.
DE   RecName: Full=Neutral protease 2 homolog MEP3;
DE            EC=3.4.24.39;
DE   AltName: Full=Deuterolysin MEP3;
DE   AltName: Full=Metalloproteinase 3;
DE   Flags: Precursor;
GN   Name=MEP3; ORFNames=CPC735_031330;
OS   Coccidioides posadasii (strain C735) (Valley fever fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Onygenaceae; Coccidioides.
OX   NCBI_TaxID=222929;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C735;
RX   PubMed=16177346; DOI=10.1128/iai.73.10.6689-6703.2005;
RA   Hung C.Y., Seshan K.R., Yu J.J., Schaller R., Xue J., Basrur V.,
RA   Gardner M.J., Cole G.T.;
RT   "A metalloproteinase of Coccidioides posadasii contributes to evasion of
RT   host detection.";
RL   Infect. Immun. 73:6689-6703(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C735;
RX   PubMed=19717792; DOI=10.1101/gr.087551.108;
RA   Sharpton T.J., Stajich J.E., Rounsley S.D., Gardner M.J., Wortman J.R.,
RA   Jordar V.S., Maiti R., Kodira C.D., Neafsey D.E., Zeng Q., Hung C.-Y.,
RA   McMahan C., Muszewska A., Grynberg M., Mandel M.A., Kellner E.M.,
RA   Barker B.M., Galgiani J.N., Orbach M.J., Kirkland T.N., Cole G.T.,
RA   Henn M.R., Birren B.W., Taylor J.W.;
RT   "Comparative genomic analyses of the human fungal pathogens Coccidioides
RT   and their relatives.";
RL   Genome Res. 19:1722-1731(2009).
CC   -!- FUNCTION: Secreted metalloproteinase that allows assimilation of
CC       proteinaceous substrates. Shows high activities on basic nuclear
CC       substrates such as histone and protamine. May be involved in virulence
CC       (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M35 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAY45753.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AY987807; AAY45753.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; ACFW01000025; EER27797.1; -; Genomic_DNA.
DR   RefSeq; XP_003069942.1; XM_003069896.1.
DR   AlphaFoldDB; C5P507; -.
DR   SMR; C5P507; -.
DR   EnsemblFungi; EER27797; EER27797; CPC735_031330.
DR   GeneID; 9695437; -.
DR   KEGG; cpw:CPC735_031330; -.
DR   VEuPathDB; FungiDB:CPC735_031330; -.
DR   HOGENOM; CLU_039313_1_1_1; -.
DR   BRENDA; 3.4.24.39; 9184.
DR   Proteomes; UP000009084; Unassembled WGS sequence.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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; IPR029463; Lys_MEP.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001384; Peptidase_M35.
DR   Pfam; PF02102; Peptidase_M35; 1.
DR   PRINTS; PR00768; DEUTEROLYSIN.
DR   SMART; SM01351; Aspzincin_M35; 1.
PE   3: Inferred from homology;
KW   Cleavage on pair of basic residues; Disulfide bond; Hydrolase;
KW   Metal-binding; Metalloprotease; Protease; Secreted; Signal; Virulence;
KW   Zinc; Zymogen.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..179
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000407068"
FT   CHAIN           180..354
FT                   /note="Neutral protease 2 homolog MEP3"
FT                   /id="PRO_0000407069"
FT   ACT_SITE        306
FT                   /evidence="ECO:0000250"
FT   BINDING         305
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         309
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         320
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   DISULFID        186..256
FT                   /evidence="ECO:0000250"
FT   DISULFID        263..281
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   354 AA;  37918 MW;  DE6EE7BA166B79D7 CRC64;
     MHFTSSLLAL VALTTQALAF PLNDLPKRDS GLAVKLSSIG NTRVKAVITN TADHEISFLK
     FNTFFDSSAT RKVSIAKDGS VVPFNGLYRY YNAAKLPKEA FKTLAPGASA EATFDIAETS
     DLSAGGSFSV FSDGMIPVAD GSGTTLTGAI KYSTNELKMN VDGALAAKVQ SAIPKLEKRT
     RIDPDCPGEY RNVLTQGLQT AAGYASRAAE AATNGDQLEE FFKTTDQQTA QNIAQRFQAI
     AQECGSDSQG STTYFCDDRF NGCEQGVIAY TIPAQSVVVN CPAYWELPPV VNQGLDPDHG
     YVVVHEFTHA TSIFSPGTQD HAYGYENCIR LSPEQCISNA DNYSLYAASV SRGG