ID   MEP8_COCP7              Reviewed;         358 AA.
AC   C5NZL6; Q3KRQ5;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-SEP-2009, sequence version 1.
DT   03-AUG-2022, entry version 51.
DE   RecName: Full=Neutral protease 2 homolog MEP8;
DE            EC=3.4.24.39;
DE   AltName: Full=Deuterolysin MEP8;
DE   AltName: Full=Metalloproteinase 8;
DE   Flags: Precursor;
GN   Name=MEP8; ORFNames=CPC735_012270;
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}.
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DR   EMBL; AY987812; AAY45758.1; -; Genomic_DNA.
DR   EMBL; ACFW01000001; EER29909.1; -; Genomic_DNA.
DR   RefSeq; XP_003072054.1; XM_003072008.1.
DR   AlphaFoldDB; C5NZL6; -.
DR   SMR; C5NZL6; -.
DR   EnsemblFungi; EER29909; EER29909; CPC735_012270.
DR   GeneID; 9697549; -.
DR   KEGG; cpw:CPC735_012270; -.
DR   VEuPathDB; FungiDB:CPC735_012270; -.
DR   HOGENOM; CLU_039313_1_0_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; 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   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_0000407078"
FT   CHAIN           180..358
FT                   /note="Neutral protease 2 homolog MEP8"
FT                   /id="PRO_0000407079"
FT   ACT_SITE        306
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         305
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         309
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         320
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   DISULFID        186..256
FT                   /evidence="ECO:0000250"
FT   DISULFID        263..281
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   358 AA;  39707 MW;  C91C90C03C94FAEB CRC64;
     MKLSSILLAL AALVSPAFSY AISHLPRSEG GLDIKLTAIG NTRIKAIITN KADRPLKLLR
     YNNFFDDAPT QKVEIFKDGN AVQFEGIYQH IYMTDLPDED FISLTPGESI EREVDIATTA
     DLTQGGAFTI SSQGLIPFAE VDSNEVTGAM AFHANDLEMD VDGAVAATVE KAIKPVDKRS
     RLTNSCTGQR RTATVRAIQA SAQLSQRSAQ VAQNNAQKLQ EYFKQTDQRT RQLVVNRFTA
     VARESTVNGG RTTYDCTDRM GHCQPRTIAY TLPAQNHITN CPIFYQMPLL TNRCHGQDQA
     TTVLHEITHN PAIVQPHCVD HGYGYQAVRR LNAQQSLQNA DTYSLFANGK MTFRLFLY