ID   MEP4_COCP7              Reviewed;         412 AA.
AC   C5PIJ9; Q3KRQ9;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-SEP-2009, sequence version 1.
DT   03-AUG-2022, entry version 54.
DE   RecName: Full=Neutral protease 2 homolog MEP4;
DE            EC=3.4.24.39;
DE   AltName: Full=Deuterolysin MEP4;
DE   AltName: Full=Metalloproteinase 4;
DE   Flags: Precursor;
GN   Name=MEP4; ORFNames=CPC735_057220;
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=AAY45754.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AY987808; AAY45754.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; ACFW01000049; EER24352.1; -; Genomic_DNA.
DR   RefSeq; XP_003066497.1; XM_003066451.1.
DR   AlphaFoldDB; C5PIJ9; -.
DR   SMR; C5PIJ9; -.
DR   EnsemblFungi; EER24352; EER24352; CPC735_057220.
DR   GeneID; 9691967; -.
DR   KEGG; cpw:CPC735_057220; -.
DR   VEuPathDB; FungiDB:CPC735_057220; -.
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; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001384; Peptidase_M35.
DR   Pfam; PF02102; Peptidase_M35; 1.
DR   PRINTS; PR00768; DEUTEROLYSIN.
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..17
FT                   /evidence="ECO:0000255"
FT   PROPEP          18..183
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000407070"
FT   CHAIN           184..412
FT                   /note="Neutral protease 2 homolog MEP4"
FT                   /id="PRO_0000407071"
FT   ACT_SITE        312
FT                   /evidence="ECO:0000250"
FT   BINDING         311
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         315
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         326
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   DISULFID        191..263
FT                   /evidence="ECO:0000250"
FT   DISULFID        268..286
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   412 AA;  45091 MW;  307D5EA38693D293 CRC64;
     MFATAIVAVL LAAASSAFPH AAREASKDDA NVSVQLSAVG NTMVKAVVTN RGDEAISVLR
     LNSVLDSFPC RRVDVYKEGK KMEFEGLLAH HDMQNLPDDV FATLNPGDFA ENTFDIAETV
     DLSAGGPVTV LSEGVFLLAR SDSTSISGMV QYRSNELKID VDGVLAAKVE SAGGLRRRNL
     DKRTSFYLDT CTPAAMKNLT ALLKSTTDYA DAGARAATNG SLATFETFFK KTDLRTRRPV
     ASRFRAISNE TSIIDGGIVR LTCSDDFCKG TINAIADSWI SFITICPRFF SAYPPTSPEC
     HATDQTSILL HEMTHMRHVY SPGTNDFAYG YDNVTKLPAD QAINNADTFA IYAAGKFFFF
     WFFVPYPIAS SIPGLIYFHR FLPWMLNGKV IGTCRRCMPT SLLRRHLGGK SL