ID   MEP6_COCP7              Reviewed;         355 AA.
AC   C5PE18; Q3KRQ7;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-SEP-2009, sequence version 1.
DT   03-AUG-2022, entry version 52.
DE   RecName: Full=Neutral protease 2 homolog MEP6;
DE            EC=3.4.24.39;
DE   AltName: Full=Deuterolysin MEP6;
DE   AltName: Full=Metalloproteinase 6;
DE   Flags: Precursor;
GN   Name=MEP6; ORFNames=CPC735_019360;
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=AAY45756.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AY987810; AAY45756.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; ACFW01000043; EER25329.1; -; Genomic_DNA.
DR   RefSeq; XP_003067474.1; XM_003067428.1.
DR   AlphaFoldDB; C5PE18; -.
DR   SMR; C5PE18; -.
DR   EnsemblFungi; EER25329; EER25329; CPC735_019360.
DR   GeneID; 9692945; -.
DR   KEGG; cpw:CPC735_019360; -.
DR   VEuPathDB; FungiDB:CPC735_019360; -.
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.
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_0000407074"
FT   CHAIN           180..355
FT                   /note="Neutral protease 2 homolog MEP6"
FT                   /id="PRO_0000407075"
FT   ACT_SITE        308
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         307
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         311
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         322
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   DISULFID        187..259
FT                   /evidence="ECO:0000250"
FT   DISULFID        266..283
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   355 AA;  38657 MW;  50D49AAC134F13A1 CRC64;
     MRLSSSLIAL VALAGQALAL PFNELAERDT GLDVKLIPIG NTRVKAIITN NADHEMSFVK
     YNTLFDSSPV RKVQISKDGS IIPFKGIHLY YDIDNLPKEA YKTLAPGASA EAEFDIAETS
     DLSAGGSFKI SAEGSIPVID GQGTKPTSSI RFKANTLTMD IDGEMASRVA SAIPELNKRT
     RVDNQTCTGQ YAQLLQGGLR TCATYAQRAA QAASGGNAQK FQEYFKTTNQ QTRQNVARRF
     QAIAQECSSA NQGRTIYFCQ DVYGYCQGAI AYTVPDRSHV VNCPAYWSLP PVLNRGLGPD
     HGYVIVHEFT HAPSVFSPGT VDHAYGYEQC RRLNAQQSLN NADSYSLFAA DVSRN