ID   CYT_AUSSU               Reviewed;         141 AA.
AC   E3P6N3;
DT   24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 1.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=AsCystatin;
DE            Short=AsCys;
DE            Short=Cystatin;
DE   Flags: Precursor;
OS   Austrelaps superbus (Lowland copperhead snake) (Hoplocephalus superbus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Acanthophiinae; Austrelaps.
OX   NCBI_TaxID=29156;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, LEVEL OF PROTEIN EXPRESSION,
RP   3D-STRUCTURE MODELING IN COMPLEX WITH A CYSTEINE PROTEASE, AND MUTAGENESIS
RP   OF GLY-29.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=21172403; DOI=10.1016/j.biochi.2010.12.008;
RA   Richards R., St Pierre L., Trabi M., Johnson L.A., de Jersey J.,
RA   Masci P.P., Lavin M.F.;
RT   "Cloning and characterisation of novel cystatins from elapid snake venom
RT   glands.";
RL   Biochimie 93:659-668(2011).
CC   -!- FUNCTION: Recombinant AsCystatin inhibits various C1 cysteine proteases
CC       including cathepsin L (Ki is 0.89 pM), papain (Ki is 1.74 pM) and
CC       cathepsin B (Ki is 0.69 nM). This activity has also been observed in
CC       the crude venom. This protein has no toxic activity and its function in
CC       the venom is unknown. It may play a role as a housekeeping or
CC       regulatory protein. {ECO:0000269|PubMed:21172403}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed at a low level by the venom gland (at
CC       protein level). {ECO:0000305|PubMed:21172403}.
CC   -!- MISCELLANEOUS: The recombinant protein does not inhibit calpain-1
CC       (CAPN1), a C2 family cysteine protease and legumain (LGMN), a C13
CC       family cysteine protease. Does not provoke cell death (PC3 prostate
CC       cancer cells) following continuous exposure to 6 uM for 24 hours
CC       (PubMed:21172403). {ECO:0000305|PubMed:21172403}.
CC   -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
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DR   EMBL; FJ411278; ACR83839.1; -; mRNA.
DR   AlphaFoldDB; E3P6N3; -.
DR   SMR; E3P6N3; -.
DR   MEROPS; I25.012; -.
DR   PRIDE; E3P6N3; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   CDD; cd00042; CY; 1.
DR   InterPro; IPR000010; Cystatin_dom.
DR   InterPro; IPR046350; Cystatin_sf.
DR   Pfam; PF00031; Cystatin; 1.
DR   SMART; SM00043; CY; 1.
DR   SUPFAM; SSF54403; SSF54403; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Protease inhibitor; Secreted; Signal;
KW   Thiol protease inhibitor.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000250"
FT   CHAIN           27..141
FT                   /note="AsCystatin"
FT                   /id="PRO_5000654409"
FT   DOMAIN          29..129
FT                   /note="Cystatin"
FT   MOTIF           73..77
FT                   /note="Secondary area of contact"
FT                   /evidence="ECO:0000250"
FT   SITE            29
FT                   /note="Reactive site"
FT                   /evidence="ECO:0000250"
FT   DISULFID        91..107
FT                   /evidence="ECO:0000250"
FT   DISULFID        120..140
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         29
FT                   /note="G->S: 1000-fold reduction in inhibitory activity
FT                   tested on papain."
FT                   /evidence="ECO:0000269|PubMed:21172403"
SQ   SEQUENCE   141 AA;  15855 MW;  42CC622B56FF34F0 CRC64;
     MVHSQLPVAA PLRLLCALLL LPLATMIPGG LSPRSVTDPD VQEAAEFAVQ EYNALSANAY
     YYKQLRIVEA QSQVVTGAKY YLTMELMKTK CAKTTGKPKV YKEIQNCELP PKAQQEKLTC
     RFQVWSCPWL QKIELTKMSC N