ID   SUB2_PSED2              Reviewed;         400 AA.
AC   L8FSM5;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 1.
DT   03-AUG-2022, entry version 39.
DE   RecName: Full=Subtilisin-like protease 2 {ECO:0000250|UniProtKB:L8G6I7};
DE            EC=3.4.21.- {ECO:0000305|PubMed:25944934};
DE   AltName: Full=Destructin-1 {ECO:0000303|PubMed:25944934};
DE   AltName: Full=Serine protease 2 {ECO:0000303|PubMed:25785714};
DE            Short=PdSP2 {ECO:0000303|PubMed:25785714};
DE   Flags: Precursor;
GN   Name=SP2 {ECO:0000303|PubMed:25785714}; ORFNames=GMDG_06417;
OS   Pseudogymnoascus destructans (strain ATCC MYA-4855 / 20631-21) (Bat
OS   white-nose syndrome fungus) (Geomyces destructans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC   Leotiomycetes incertae sedis; Pseudeurotiaceae; Pseudogymnoascus.
OX   NCBI_TaxID=658429;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4855 / 20631-21;
RG   The Broad Institute Genome Sequencing Platform;
RA   Cuomo C.A., Blehert D.S., Lorch J.M., Young S.K., Zeng Q., Gargeya S.,
RA   Fitzgerald M., Haas B., Abouelleil A., Alvarado L., Arachchi H.M.,
RA   Berlin A., Brown A., Chapman S.B., Chen Z., Dunbar C., Freedman E.,
RA   Gearin G., Gellesch M., Goldberg J., Griggs A., Gujja S., Heiman D.,
RA   Howarth C., Larson L., Lui A., MacDonald P.J.P., Montmayeur A., Murphy C.,
RA   Neiman D., Pearson M., Priest M., Roberts A., Saif S., Shea T., Shenoy N.,
RA   Sisk P., Stolte C., Sykes S., Wortman J., Nusbaum C., Birren B.;
RT   "The genome sequence of Geomyces destructans 20631-21.";
RL   Submitted (SEP-2010) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF N-TERMINUS, PROTEOLYTIC CLEAVAGE, FUNCTION, CATALYTIC
RP   ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR
RP   LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25944934; DOI=10.1073/pnas.1507082112;
RA   O'Donoghue A.J., Knudsen G.M., Beekman C., Perry J.A., Johnson A.D.,
RA   DeRisi J.L., Craik C.S., Bennett R.J.;
RT   "Destructin-1 is a collagen-degrading endopeptidase secreted by
RT   Pseudogymnoascus destructans, the causative agent of white-nose syndrome.";
RL   Proc. Natl. Acad. Sci. U.S.A. 112:7478-7483(2015).
RN   [3]
RP   ERRATUM OF PUBMED:25944934.
RX   PubMed=26015578; DOI=10.1073/pnas.1509071112;
RA   O'Donoghue A.J., Knudsen G.M., Beekman C., Perry J.A., Johnson A.D.,
RA   DeRisi J.L., Craik C.S., Bennett R.J.;
RL   Proc. Natl. Acad. Sci. U.S.A. 112:E3152-E3152(2015).
RN   [4]
RP   GENE NAME.
RX   PubMed=25785714; DOI=10.1371/journal.pone.0120508;
RA   Pannkuk E.L., Risch T.S., Savary B.J.;
RT   "Isolation and identification of an extracellular subtilisin-like serine
RT   protease secreted by the bat pathogen Pseudogymnoascus destructans.";
RL   PLoS ONE 10:E0120508-E0120508(2015).
CC   -!- FUNCTION: Major secreted subtilisin-like serine endopeptidase.
CC       Preferentially cleaves substrates containing hydrophobic residues at
CC       P4, positively charged residues at P3, small or flexible residues at
CC       P2, and large, bulky residues at P1. Mediates the degradation of
CC       collagen, the major structural protein in the mammalian host. Degrades
CC       the nonhelical regions of collagen that function in the cross-linking
CC       of the helical components (PubMed:25944934). May function as virulence
CC       factor involved in epidermal wing necrosis observed in white nose
CC       syndrome (WNS) in bats (By similarity). {ECO:0000250|UniProtKB:L8G6I7,
CC       ECO:0000269|PubMed:25944934}.
CC   -!- ACTIVITY REGULATION: Potently inhibited by the serine peptidase
CC       inhibitor chymostatin. Also inhibited by antpain and PMSF.
CC       {ECO:0000269|PubMed:25944934}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 9-10. {ECO:0000269|PubMed:25944934};
CC       Temperature dependence:
CC         Optimum temperature is 20-30 degrees Celsius.;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25944934}.
CC   -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR   EMBL; GL573328; ELR03877.1; -; Genomic_DNA.
DR   RefSeq; XP_012744855.1; XM_012889401.1.
DR   AlphaFoldDB; L8FSM5; -.
DR   SMR; L8FSM5; -.
DR   STRING; 658429.L8FSM5; -.
DR   EnsemblFungi; ELR03877; ELR03877; GMDG_06417.
DR   VEuPathDB; FungiDB:GMDG_06417; -.
DR   HOGENOM; CLU_011263_1_4_1; -.
DR   InParanoid; L8FSM5; -.
DR   OrthoDB; 308083at2759; -.
DR   Proteomes; UP000011064; Unassembled WGS sequence.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd04077; Peptidases_S8_PCSK9_ProteinaseK_like; 1.
DR   Gene3D; 3.30.70.80; -; 1.
DR   Gene3D; 3.40.50.200; -; 1.
DR   InterPro; IPR034193; PCSK9_ProteinaseK-like.
DR   InterPro; IPR000209; Peptidase_S8/S53_dom.
DR   InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR   InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR   InterPro; IPR022398; Peptidase_S8_His-AS.
DR   InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR   InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR   InterPro; IPR010259; S8pro/Inhibitor_I9.
DR   InterPro; IPR037045; S8pro/Inhibitor_I9_sf.
DR   Pfam; PF05922; Inhibitor_I9; 1.
DR   Pfam; PF00082; Peptidase_S8; 1.
DR   PRINTS; PR00723; SUBTILISIN.
DR   SUPFAM; SSF52743; SSF52743; 1.
DR   PROSITE; PS51892; SUBTILASE; 1.
DR   PROSITE; PS00136; SUBTILASE_ASP; 1.
DR   PROSITE; PS00137; SUBTILASE_HIS; 1.
DR   PROSITE; PS00138; SUBTILASE_SER; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Glycoprotein; Hydrolase; Protease;
KW   Reference proteome; Secreted; Serine protease; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..119
FT                   /evidence="ECO:0000269|PubMed:25944934"
FT                   /id="PRO_0000434138"
FT   CHAIN           120..400
FT                   /note="Subtilisin-like protease 2"
FT                   /id="PRO_0000434139"
FT   DOMAIN          42..117
FT                   /note="Inhibitor I9"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          128..400
FT                   /note="Peptidase S8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        160
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        192
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        345
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   SITE            119..120
FT                   /note="Cleavage; by autocatalysis"
FT                   /evidence="ECO:0000305|PubMed:25944934"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   400 AA;  40489 MW;  1233290343D05688 CRC64;
     MKFSQSLIAL AACFLPLIAA APEEAQHAKI RSPGAQDIIL DSYIVVFNKG VNDADIESEF
     ASVSHILSKR RPAHKGVGHK YNITGFKGYQ IETDTGSIGE IAASPLVAWI ERDGKVQANA
     LETRSGATWG LGRISHKATG SNSYVYDSSA GSGSTVYVVD SGIYIEHSEF EGRAKWGANY
     ISGSPDTDEN GHGTHCAGTI AGATYGVASK ANLVAVKVLD GDGSGSNSGV IAGINFVGQN
     GKDGKSVLSM SLGGSYSAAL NSAVESTISN GVTVVVAAGN DGADASNYSP ASAKNAITVG
     AVDSTDTRAD FSNYGSVLDV FAPGVDVKSA WIGSKSASNT ISGTSMATPH VAGLAAYLIG
     LGGLSSPAAV ASKIASIGIQ GSVKDPKGSV NLIAYNGNGA